Variant rs10423288 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.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
ENST00000558518.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.566

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=-0.81).

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	Protein	UniProt
LDLR	NM_000527.5 linkuse as main transcript	c.314-50T>C		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.314-50T>C		intron_variant		1	NM_000527.5	ENSP00000454071	P3	P01130-1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9118

AN:

152066

Hom.:

478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0557

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0523

GnomAD3 exomes

AF:

0.0553

AC:

13502

AN:

244044

Hom.:

764

AF XY:

0.0491

AC XY:

6536

AN XY:

133186

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0301

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.0569

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0413

GnomAD4 exome

AF:

0.0264

AC:

38536

AN:

1458258

Hom.:

1445

Cov.:

AF XY:

0.0263

AC XY:

19086

AN XY:

725562

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.0289

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.0523

Gnomad4 FIN exome

AF:

0.0234

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0602

AC:

9154

AN:

152184

Hom.:

484

Cov.:

AF XY:

0.0608

AC XY:

4528

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0560

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.0508

Alfa

AF:

0.0482

Hom.:

100

Bravo

AF:

0.0703

Asia WGS

AF:

0.100

AC:

349

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	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	Mar 01, 2016	5/95 non-FH individuals -
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

-0.81

CADD

Benign

0.74

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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