Variant rs13306501 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000558518.6(LDLR):c.2389+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,540,490 control chromosomes in the GnomAD database, including 2,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 416 hom., cov: 31)

Exomes 𝑓: 0.054 ( 2311 hom. )

Consequence

LDLR
ENST00000558518.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.797

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:

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=-0.82).

BP6

Variant 19-11128132-G-A is Benign according to our data. Variant chr19-11128132-G-A is described in ClinVar as [Benign]. Clinvar id is 431551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11128132-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLR	NM_000527.5 linkuse as main transcript	c.2389+47G>A		intron_variant		ENST00000558518.6	NP_000518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLR	ENST00000558518.6 linkuse as main transcript	c.2389+47G>A		intron_variant		1	NM_000527.5	ENSP00000454071	P3	P01130-1

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10060

AN:

151972

Hom.:

412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.0941

Gnomad FIN

AF:

0.0400

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0632

AC:

15822

AN:

250258

Hom.:

593

AF XY:

0.0638

AC XY:

8649

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0685

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.0968

Gnomad FIN exome

AF:

0.0407

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0524

GnomAD4 exome

AF:

0.0535

AC:

74296

AN:

1388400

Hom.:

2311

Cov.:

AF XY:

0.0553

AC XY:

38396

AN XY:

694920

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0513

Gnomad4 ASJ exome

AF:

0.0683

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0981

Gnomad4 FIN exome

AF:

0.0419

Gnomad4 NFE exome

AF:

0.0462

Gnomad4 OTH exome

AF:

0.0554

GnomAD4 genome

AF:

0.0663

AC:

10084

AN:

152090

Hom.:

416

Cov.:

AF XY:

0.0656

AC XY:

4874

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0382

Gnomad4 ASJ

AF:

0.0686

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0939

Gnomad4 FIN

AF:

0.0400

Gnomad4 NFE

AF:

0.0463

Gnomad4 OTH

AF:

0.0511

Alfa

AF:

0.0608

Hom.:

Bravo

AF:

0.0681

Asia WGS

AF:

0.0650

AC:

226

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, criteria provided, single submitter	research	Laboratory of Genetics and Molecular Cardiology, University of São Paulo	Mar 01, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.53

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over