Variant 19-11116790-G-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.1706-69G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,569,414 control chromosomes in the GnomAD database, including 23,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4311 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18979 hom. )

Consequence

LDLR
NM_000527.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.85

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=-0.87).

BP6

Variant 19-11116790-G-T is Benign according to our data. Variant chr19-11116790-G-T is described in ClinVar as [Benign]. Clinvar id is 251985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11116790-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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.1706-69G>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.1706-69G>T		intron_variant		1	NM_000527.5	ENSP00000454071	P3	P01130-1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32053

AN:

152038

Hom.:

4298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.180

GnomAD4 exome

AF:

0.152

AC:

215490

AN:

1417258

Hom.:

18979

AF XY:

0.152

AC XY:

107736

AN XY:

707552

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.211

AC:

32100

AN:

152156

Hom.:

4311

Cov.:

AF XY:

0.209

AC XY:

15543

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.369

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.374

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.0925

Hom.:

151

Bravo

AF:

0.220

Asia WGS

AF:

0.223

AC:

777

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Benign:3

Benign, criteria provided, single submitter	research	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	Mar 01, 2016	3 hmz + 28 htz / 125 non-FH individuals -
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

-0.87

CADD

Benign

0.18

DANN

Benign

0.66

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