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GeneBe

rs6511720

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000527.5(LDLR):c.67+2015G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,196 control chromosomes in the GnomAD database, including 1,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1095 hom., cov: 32)

Consequence

LDLR
NM_000527.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.224
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]

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 19-11091630-G-T is Benign according to our data. Variant chr19-11091630-G-T is described in ClinVar as [Benign]. Clinvar id is 250988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11091630-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LDLRNM_000527.5 linkuse as main transcriptc.67+2015G>T intron_variant ENST00000558518.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LDLRENST00000558518.6 linkuse as main transcriptc.67+2015G>T intron_variant 1 NM_000527.5 P3P01130-1

Frequencies

GnomAD3 genomes
AF:
0.114
AC:
17315
AN:
152078
Hom.:
1098
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.135
Gnomad AMI
AF:
0.127
Gnomad AMR
AF:
0.0934
Gnomad ASJ
AF:
0.133
Gnomad EAS
AF:
0.00769
Gnomad SAS
AF:
0.0732
Gnomad FIN
AF:
0.115
Gnomad MID
AF:
0.155
Gnomad NFE
AF:
0.115
Gnomad OTH
AF:
0.116
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.114
AC:
17318
AN:
152196
Hom.:
1095
Cov.:
32
AF XY:
0.114
AC XY:
8459
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.135
Gnomad4 AMR
AF:
0.0932
Gnomad4 ASJ
AF:
0.133
Gnomad4 EAS
AF:
0.00771
Gnomad4 SAS
AF:
0.0720
Gnomad4 FIN
AF:
0.115
Gnomad4 NFE
AF:
0.115
Gnomad4 OTH
AF:
0.115
Alfa
AF:
0.114
Hom.:
2382
Bravo
AF:
0.116
Asia WGS
AF:
0.0570
AC:
200
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1 Benign:2
Benign, no assertion criteria providedresearchLaboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum-- -
Benign, criteria provided, single submitterliterature onlyLDLR-LOVD, British Heart FoundationMar 25, 2016- -
Familial hypercholesterolemia Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
3.1
Dann
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6511720; hg19: chr19-11202306; API