NM_000527.5:c.1359-1G>A

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 20 ACMG points: 20P and 0B. PS4PP1_StrongPS3_SupportingPVS1PM2PP4

This summary comes from the ClinGen Evidence Repository: The NM_000527.5(LDLR):c.1359-1G>A variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes PVS1, PP1_Strong, PS4, PM2, PP4 and PS3_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PVS1 - variant is in canonical - 1 splice site and causes a frameshift in exon 10 (p.Thr454Leufs*51, from Holla et al., 2009 (PMID 19208450)), so PVS1 is met.PP1_strong - variant segregates with FH phenotype in 9 informative meiosis from at least 5 families:- 5 informative meiosis from 4 families from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière): 5 relatives with the variant have LDL-C >75th percentile.- 4 informative meiosis from at least 1 family from Mayo lab (Mayo Clinic Atherosclerosis and Lipid Genomics Laboratory), Ambry lab (Ambry Genetics) and Arca lab (Research Lab of Molecular Genetics of Lipid Metabolism - Prof. M.Arca), but are confirmed to be the same: 2 relatives with the variant had LDL >75th percentile and 2 relatives negative for variant had LDL <50th percentile.--- so PP1_Strong is met.PS4 - variant meets PM2 and was identified in:- 25 unrelated index cases (22 cases with DLCN >=6, 3 with possible Simon Broome FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière), France;- 2 unrelated index cases (MFH101: DLCN of 8, MFH116: meets MEDPED definite) reported by Mayo lab (Mayo Clinic Atherosclerosis and Lipid Genomics Laboratory), Ambry lab (Ambry Genetics) and Arca lab (Research Lab of Molecular Genetics of Lipid Metabolism - Prof. M.Arca), but are confirmed to be the same;- 1 index case with Dutch lipid clinic network >=6 from Robarts Research Institute, Canada;- 1 index case with DLCN >= 6 from Color Health, Inc., USA.--- 29 cases (no additional bibliographic search was done because number of index cases is already over 10), so PS4 is met.PM2 - PopMax MAF = 0.00002940 (0.003%) in European non-Finnish genomes (gnomAD v3.1.2). It is below 0.02%, so PM2 is met.PP4 - variant meets PM2 and was identified in at least 29 unrelated index cases (see PS4 for details), so PP4 is met.PS3_supporting - Level 2/3 FS: Holla et al., 2009 (PMID 19208450): Htz patients' Epstein Barr virus transformed lymphocytes, RNA assays - results: skipping of the first 7 nts from exon 10 in 23% of mRNAs (p.Thr454Leufs*51)--- aberrant transcript is confirmed by sequencing and is quantified, but it is not above 25% of total transcript, so PS3_Supporting is met. LINK:https://erepo.genome.network/evrepo/ui/classification/CA023463/MONDO:0007750/013

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

LDLR
NM_000527.5 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Pathogenic reviewed by expert panel P:26

Conservation

PhyloP100: 6.43

Publications

8 publications found

Variant links:

Genes affected

LDLR (HGNC:6547): (low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]

LDLR links:

MIR6886 (HGNC:50121): (microRNA 6886) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6886 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 20 ACMG points.

PVS1

For more information check the summary or visit ClinGen Evidence Repository.

PS3

For more information check the summary or visit ClinGen Evidence Repository.

PS4

For more information check the summary or visit ClinGen Evidence Repository.

PM2

For more information check the summary or visit ClinGen Evidence Repository.

PP1

For more information check the summary or visit ClinGen Evidence Repository.

PP4

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLR	NM_000527.5 link	c.1359-1G>A		splice_acceptor_variant, intron_variant	Intron 9 of 17	ENST00000558518.6	NP_000518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLR	ENST00000558518.6 link	c.1359-1G>A		splice_acceptor_variant, intron_variant	Intron 9 of 17	1	NM_000527.5	ENSP00000454071.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

250786

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111930

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000950

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:26

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Pathogenic:15

May 10, 2022

Revvity Omics, Revvity

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 18, 2023

All of Us Research Program, National Institutes of Health

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant causes a G to A nucleotide substitution at the -1 position of intron 9 of the LDLR gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. A quantitative RNA study has shown that this variant causes a deletion of the first seven nucleotides of exon 10 due to a cryptic splice acceptor activation, and is expected to cause a frameshift and premature truncation (PMID: 10090473). This variant has been reported in hundreds of individuals affected with familial hypercholesterolemia (PMID: 7616128, 9254862, 10090473, 10735632, 11668640, 11857755, 12436241, 15241806, 21382890, 21475731, 25154303, 33955087, 34037665). It has been shown that this variant segregates with disease in multiple affected individuals in two families (PMID: 9254862, 25154303). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of LDLR function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Institute for Integrative and Experimental Genomics, University of Luebeck

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Mar 30, 2017

U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 28, 2022

ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel

Significance:Pathogenic

Review Status:reviewed by expert panel

Collection Method:curation

The NM_000527.5(LDLR):c.1359-1G>A variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes PVS1, PP1_Strong, PS4, PM2, PP4 and PS3_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PVS1 - variant is in canonical - 1 splice site and causes a frameshift in exon 10 (p.Thr454Leufs*51, from Holla et al., 2009 (PMID 19208450)), so PVS1 is met. PP1_strong - variant segregates with FH phenotype in 9 informative meiosis from at least 5 families: - 5 informative meiosis from 4 families from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière): 5 relatives with the variant have LDL-C >75th percentile. - 4 informative meiosis from at least 1 family from Mayo lab (Mayo Clinic Atherosclerosis and Lipid Genomics Laboratory), Ambry lab (Ambry Genetics) and Arca lab (Research Lab of Molecular Genetics of Lipid Metabolism - Prof. M.Arca), but are confirmed to be the same: 2 relatives with the variant had LDL >75th percentile and 2 relatives negative for variant had LDL <50th percentile. --- so PP1_Strong is met. PS4 - variant meets PM2 and was identified in: - 25 unrelated index cases (22 cases with DLCN >=6, 3 with possible Simon Broome FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière), France; - 2 unrelated index cases (MFH101: DLCN of 8, MFH116: meets MEDPED definite) reported by Mayo lab (Mayo Clinic Atherosclerosis and Lipid Genomics Laboratory), Ambry lab (Ambry Genetics) and Arca lab (Research Lab of Molecular Genetics of Lipid Metabolism - Prof. M.Arca), but are confirmed to be the same; - 1 index case with Dutch lipid clinic network >=6 from Robarts Research Institute, Canada; - 1 index case with DLCN >= 6 from Color Health, Inc., USA. --- 29 cases (no additional bibliographic search was done because number of index cases is already over 10), so PS4 is met. PM2 - PopMax MAF = 0.00002940 (0.003%) in European non-Finnish genomes (gnomAD v3.1.2). It is below 0.02%, so PM2 is met. PP4 - variant meets PM2 and was identified in at least 29 unrelated index cases (see PS4 for details), so PP4 is met. PS3_supporting - Level 2/3 FS: Holla et al., 2009 (PMID 19208450): Htz patients' Epstein Barr virus transformed lymphocytes, RNA assays - results: skipping of the first 7 nts from exon 10 in 23% of mRNAs (p.Thr454Leufs*51) --- aberrant transcript is confirmed by sequencing and is quantified, but it is not above 25% of total transcript, so PS3_Supporting is met. -

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Dec 16, 2016

Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

subjects mutated among 2600 FH index cases screened = 11 , family members = 2 with co-segregation / previously described in association with FH -

Mar 01, 2016

Fundacion Hipercolesterolemia Familiar

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 17, 2014

Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Robarts Research Institute, Western University

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 07, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2023

Zotz-Klimas Genetics Lab, MVZ Zotz Klimas

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 25, 2016

LDLR-LOVD, British Heart Foundation

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:literature only

- -

Institute of Human Genetics, University Hospital of Duesseldorf

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not provided

Pathogenic:5

Jul 29, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PP1_strong, PP4, PM2, PS3_supporting, PS4, PVS1_strong -

Jul 18, 2023

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The LDLR c.1359-1G>A variant disrupts a canonical splice-acceptor site and interferes with normal LDLR mRNA splicing. This variant has been reported in the published literature in individuals affected with hypercholesterolemia (PMIDs: 11857755 (2002), 11668640 (2001), 10735632 (2000), 7616128 (1995)). The variant has been reported to segregate with hypercholesterolemia in an affected family (PMID: 9254862 (1997). A functional study indicates that this variant impacts protein function (PMID: 19208450 (2009)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 18, 2023

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; One of the most common pathogenic variants associated with FH in the Netherlands (Lombardi et al., 2000; Holla et al., 2009; Kusters et al., 2011; van der Graaf et al., 2011; Kindt et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); Functional studies suggest activation of a cryptic splice site resulting in a frameshift and premature stop codon (Rodningen et al., 1999; Holla et al., 2009); This variant is associated with the following publications: (PMID: 25637381, 21310417, 21382890, 21475731, 15199436, 22390909, 25525159, 9254862, 24507775, 11668640, 11857755, 12436241, 15241806, 15556094, 23936638, 31447099, 26036859, 33303402, 32041611, 33740630, 34037665, 34040191, 33955087, 35379577, 35913489, 10090473, 19208450, 7616128, 10735632, 9925649, 25154303) -

Clinical Genetics, Academic Medical Center

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Familial hypercholesterolemia

Pathogenic:2

Jun 15, 2023

Color Diagnostics, LLC DBA Color Health

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change affects an acceptor splice site in intron 9 of the LDLR gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with familial hypercholesterolemia (PMID: 9254862, 10735632, 11668640, 11857755, 15241806, 21382890, 21475731, 22390909, 25154303). It has also been observed to segregate with disease in related individuals. Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this LDLR variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 363,995 individuals referred to our laboratory for LDLR testing. ClinVar contains an entry for this variant (Variation ID: 162499). Studies have shown that disruption of this splice site results in activation of a cryptic acceptor splice site, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 10090473). For these reasons, this variant has been classified as Pathogenic. -

Homozygous familial hypercholesterolemia

Pathogenic:1

Dec 23, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1359-1G>A variant in LDLR has been reported in >80 individuals with famili al hypercholesterolemia (FH), segregated with disease in 8 affected relatives fr om 3 families (Peeters 1995, Lombarid 1995 and 2000, Garcia-Garcia 2001, Braenne 2015), and has been identified in 1/8600 European American chromosomes by the N HLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs139617 694). This variant occurs in the invariant region (+/- 1,2) of the splice consen sus sequence and is predicted to cause altered splicing leading to an abnormal o r absent protein. Heterozygous loss of LDLR function is an established disease m echanism in familial hypercholesterolemia. In summary, this variant meets our cr iteria to be classified as pathogenic for familial hypercholesterolemia in an au tosomal dominant manner. ACMG/AMP criteria applied: PVS1, PP1_S, PS4, PM2 (Richa rds 2015). -

Hypercholesterolemia

Pathogenic:1

Jun 01, 2014

CSER _CC_NCGL, University of Washington

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

See cases

Pathogenic:1

Dec 08, 2021

Institute of Human Genetics, University Hospital Muenster

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ACMG categories: PVS1,PM2,PP4 -

Cardiovascular phenotype

Pathogenic:1

Jun 10, 2022

Ambry Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1359-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 10 of the LDLR gene. This alteration has been previously reported in unrelated individuals, as well as co-segregating in families, with hypercholesterolemia and has been reported as originating in the Netherlands (Peeters AV et al. Hum Genet. 1997;100(2):266-70; Kusters DM et al. Neth Heart J. 2011;19(4):175-182; Brænne I et al. BMC Cardiovasc Disord. 2014;14:108; Brænne I et al. Eur. J. Hum. Genet., 2016 Feb;24:191-7). One functional study suggested this alteration results in a partial loss of mRNA, while another study reported this alteration as causing aberrant splicing in which the first 7 base pairs of exon 10 were deleted, predicting an early stop codon (Peeters AV et al. Hum Genet. 1997;100(2):266-70; Rødningen OK et al. Hum Mutat. 1999;13(3):186-96). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

PhyloP100

6.4

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.92

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.98

Position offset: 8

DS_AL_spliceai

1.0

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over