Variant 19-11113481-C-T 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 NM_000527.5(LDLR):c.1358+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,613,508 control chromosomes in the GnomAD database, including 876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 432 hom., cov: 29)

Exomes 𝑓: 0.011 ( 444 hom. )

Consequence

LDLR
NM_000527.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.421

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:

LDLR (HGNC:):

LDLR links:

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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 19-11113481-C-T is Benign according to our data. Variant chr19-11113481-C-T is described in ClinVar as [Benign]. Clinvar id is 413776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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.1358+32C>T		intron_variant		ENST00000558518.6	NP_000518.1	P01130-1A0A024R7D5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLR	ENST00000558518.6 linkuse as main transcript	c.1358+32C>T		intron_variant		1	NM_000527.5	ENSP00000454071.1		P01130-1

Frequencies

GnomAD3 genomes

AF:

0.0446

AC:

6782

AN:

152068

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.0396

GnomAD3 exomes

AF:

0.0155

AC:

3892

AN:

250884

Hom.:

185

AF XY:

0.0129

AC XY:

1755

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00833

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0109

AC:

15932

AN:

1461322

Hom.:

444

Cov.:

AF XY:

0.0103

AC XY:

7496

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.00408

Gnomad4 FIN exome

AF:

0.00196

Gnomad4 NFE exome

AF:

0.00789

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0448

AC:

6817

AN:

152186

Hom.:

432

Cov.:

AF XY:

0.0438

AC XY:

3259

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.0392

Alfa

AF:

0.0231

Hom.:

Bravo

AF:

0.0502

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial hypercholesterolemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Hypercholesterolemia, familial, 1

Benign:1

Benign, criteria provided, single submitter

research

Laboratory of Genetics and Molecular Cardiology, University of São Paulo

Mar 01, 2016

- -

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

1.0

DANN

Benign

0.41

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