Variant chr14-100729185-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003836.7(DLK1):c.262+119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 1,488,892 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 57 hom. )

Consequence

DLK1
NM_003836.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.413

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-100729185-C-T is Benign according to our data. Variant chr14-100729185-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644535.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLK1	NM_003836.7 linkuse as main transcript	c.262+119C>T		intron_variant		ENST00000341267.9	NP_003827.4
DLK1	NM_001317172.2 linkuse as main transcript	c.262+119C>T		intron_variant			NP_001304101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLK1	ENST00000341267.9 linkuse as main transcript	c.262+119C>T		intron_variant		1	NM_003836.7	ENSP00000340292	P1	P80370-1
DLK1	ENST00000331224.10 linkuse as main transcript	c.262+119C>T		intron_variant		1		ENSP00000331081		P80370-2
DLK1	ENST00000556051.1 linkuse as main transcript	c.381C>T	p.Ser127=	synonymous_variant	3/3	2		ENSP00000450821
DLK1	ENST00000392848.9 linkuse as main transcript	c.262+119C>T		intron_variant		4		ENSP00000376589

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

964

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00679

AC:

1270

AN:

187154

Hom.:

AF XY:

0.00623

AC XY:

637

AN XY:

102202

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.0000680

Gnomad SAS exome

AF:

0.00205

Gnomad FIN exome

AF:

0.00604

Gnomad NFE exome

AF:

0.00952

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.00689

AC:

9208

AN:

1336556

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

4652

AN XY:

667352

show subpopulations

Gnomad4 AFR exome

AF:

0.000835

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.0293

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.00742

Gnomad4 OTH exome

AF:

0.00652

GnomAD4 genome

AF:

0.00633

AC:

964

AN:

152336

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

456

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.00515

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

DLK1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

DANN

Benign

0.46

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