rs10423288
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000527.5(LDLR):c.314-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,610,442 control chromosomes in the GnomAD database, including 1,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.060 ( 484 hom., cov: 33)
Exomes 𝑓: 0.026 ( 1445 hom. )
Consequence
LDLR
NM_000527.5 intron
NM_000527.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.566
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 19-11105170-T-C is Benign according to our data. Variant chr19-11105170-T-C is described in ClinVar as [Benign]. Clinvar id is 265898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11105170-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.314-50T>C | intron_variant | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.314-50T>C | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0600 AC: 9118AN: 152066Hom.: 478 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
9118
AN:
152066
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0553 AC: 13502AN: 244044Hom.: 764 AF XY: 0.0491 AC XY: 6536AN XY: 133186
GnomAD3 exomes
AF:
AC:
13502
AN:
244044
Hom.:
AF XY:
AC XY:
6536
AN XY:
133186
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0264 AC: 38536AN: 1458258Hom.: 1445 Cov.: 33 AF XY: 0.0263 AC XY: 19086AN XY: 725562
GnomAD4 exome
AF:
AC:
38536
AN:
1458258
Hom.:
Cov.:
33
AF XY:
AC XY:
19086
AN XY:
725562
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0602 AC: 9154AN: 152184Hom.: 484 Cov.: 33 AF XY: 0.0608 AC XY: 4528AN XY: 74414
GnomAD4 genome
?
AF:
AC:
9154
AN:
152184
Hom.:
Cov.:
33
AF XY:
AC XY:
4528
AN XY:
74414
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
349
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Benign, criteria provided, single submitter | research | Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge | Mar 01, 2016 | 5/95 non-FH individuals - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at