Variant 19-11116268-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 ENST00000558518.6(LDLR):c.1705+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,149,754 control chromosomes in the GnomAD database, including 18,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4568 hom., cov: 33)

Exomes 𝑓: 0.15 ( 14190 hom. )

Consequence

LDLR
ENST00000558518.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.15

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=-0.86).

BP6

Variant 19-11116268-C-T is Benign according to our data. Variant chr19-11116268-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 251983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11116268-C-T is described in Lovd as [Benign]. Variant chr19-11116268-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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.1705+56C>T		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.1705+56C>T		intron_variant		1	NM_000527.5	ENSP00000454071	P3	P01130-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32698

AN:

152050

Hom.:

4552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.182

GnomAD4 exome

AF:

0.153

AC:

152900

AN:

997586

Hom.:

14190

AF XY:

0.154

AC XY:

79333

AN XY:

515594

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.404

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.215

AC:

32752

AN:

152168

Hom.:

4568

Cov.:

AF XY:

0.213

AC XY:

15851

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.375

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.148

Hom.:

3746

Bravo

AF:

0.225

Asia WGS

AF:

0.226

AC:

790

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Benign:2

Likely benign, criteria provided, single submitter	literature only	LDLR-LOVD, British Heart Foundation	Mar 25, 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

-0.86

CADD

Benign

0.68

DANN

Benign

0.49

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