19-11123327-T-G
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate
The NM_000527.5(LDLR):c.2294T>G(p.Val765Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
LDLR
NM_000527.5 missense
NM_000527.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 0.537
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39921418).
BP6
Variant 19-11123327-T-G is Benign according to our data. Variant chr19-11123327-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 252266.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11123327-T-G is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.2294T>G | p.Val765Gly | missense_variant | Exon 15 of 18 | ENST00000558518.6 | NP_000518.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251110Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135790
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461830Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727210
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GnomAD4 genome Cov.: 32
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32
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Benign:1
Mar 25, 2016
LDLR-LOVD, British Heart Foundation
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.;.;.;M
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;.;.;.;.
Vest4
MutPred
Loss of stability (P = 0.0072);Loss of stability (P = 0.0072);.;.;.;Loss of stability (P = 0.0072);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at