Variant 8-13100516-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182643.3(DLC1):c.1821G>T(p.Ala607=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,611,792 control chromosomes in the GnomAD database, including 99,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7898 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92002 hom. )

Consequence

DLC1
NM_182643.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

DLC1 (HGNC:2897): (DLC1 Rho GTPase activating protein) This gene encodes a GTPase-activating protein (GAP) that is a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins. GAP family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. This gene functions as a tumor suppressor gene in a number of common cancers, including prostate, lung, colorectal, and breast cancers. Multiple transcript variants due to alternative promoters and alternative splicing have been found for this gene.[provided by RefSeq, Apr 2010]

DLC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 8-13100516-C-A is Benign according to our data. Variant chr8-13100516-C-A is described in ClinVar as [Benign]. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLC1	NM_182643.3 linkuse as main transcript	c.1821G>T	p.Ala607=	synonymous_variant	9/18	ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9 linkuse as main transcript	c.1821G>T	p.Ala607=	synonymous_variant	9/18	1	NM_182643.3	ENSP00000276297		Q96QB1-2

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45778

AN:

151660

Hom.:

7885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.587

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.347

GnomAD3 exomes

AF:

0.372

AC:

92134

AN:

248004

Hom.:

19131

AF XY:

0.361

AC XY:

48583

AN XY:

134594

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.586

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.582

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.347

AC:

506127

AN:

1460014

Hom.:

92002

Cov.:

AF XY:

0.344

AC XY:

250066

AN XY:

726394

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.593

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.302

AC:

45799

AN:

151778

Hom.:

7898

Cov.:

AF XY:

0.301

AC XY:

22345

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.587

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.315

Hom.:

2419

Bravo

AF:

0.312

Asia WGS

AF:

0.454

AC:

1577

AN:

3478

EpiCase

AF:

0.331

EpiControl

AF:

0.330

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 27, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.6

DANN

Benign

0.62

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