Variant chr14-100734308-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003836.7(DLK1):c.564T>C(p.Ile188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,613,058 control chromosomes in the GnomAD database, including 252,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.62 ( 30798 hom., cov: 33)

Exomes 𝑓: 0.54 ( 221227 hom. )

Consequence

DLK1
NM_003836.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.449

Variant links:

Genes affected

DLK1 (HGNC:2907): (delta like non-canonical Notch ligand 1) This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal. [provided by RefSeq, Nov 2015]

DLK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 14-100734308-T-C is Benign according to our data. Variant chr14-100734308-T-C is described in ClinVar as [Benign]. Clinvar id is 3059696.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.449 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLK1	NM_003836.7 linkuse as main transcript	c.564T>C	p.Ile188=	synonymous_variant	5/5	ENST00000341267.9	NP_003827.4
DLK1	NM_001317172.2 linkuse as main transcript	c.564T>C	p.Ile188=	synonymous_variant	5/6		NP_001304101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLK1	ENST00000341267.9 linkuse as main transcript	c.564T>C	p.Ile188=	synonymous_variant	5/5	1	NM_003836.7	ENSP00000340292	P1	P80370-1
DLK1	ENST00000331224.10 linkuse as main transcript	c.564T>C	p.Ile188=	synonymous_variant	5/6	1		ENSP00000331081		P80370-2

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94432

AN:

151990

Hom.:

30742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.738

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.629

AC:

157523

AN:

250360

Hom.:

52434

AF XY:

0.616

AC XY:

83541

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.745

Gnomad AMR exome

AF:

0.766

Gnomad ASJ exome

AF:

0.550

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.681

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.539

AC:

787008

AN:

1460952

Hom.:

221227

Cov.:

AF XY:

0.539

AC XY:

392117

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.752

Gnomad4 AMR exome

AF:

0.751

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.672

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.622

AC:

94548

AN:

152106

Hom.:

30798

Cov.:

AF XY:

0.633

AC XY:

47033

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.739

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.552

Gnomad4 EAS

AF:

0.996

Gnomad4 SAS

AF:

0.650

Gnomad4 FIN

AF:

0.687

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.601

Alfa

AF:

0.528

Hom.:

42346

Bravo

AF:

0.624

Asia WGS

AF:

0.854

AC:

2967

AN:

3478

EpiCase

AF:

0.490

EpiControl

AF:

0.489

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLK1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.0

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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