Variant rs532841 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 ENST00000276297.9(DLC1):c.2371G>A(p.Val791Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,612,378 control chromosomes in the GnomAD database, including 200,609 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.51 ( 20515 hom., cov: 32)

Exomes 𝑓: 0.49 ( 180094 hom. )

Consequence

DLC1
ENST00000276297.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.564

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1031931E-5).

BP6

Variant 8-13099966-C-T is Benign according to our data. Variant chr8-13099966-C-T is described in ClinVar as [Benign]. Clinvar id is 1573575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 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.2371G>A	p.Val791Met	missense_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.2371G>A	p.Val791Met	missense_variant	9/18	1	NM_182643.3	ENSP00000276297		Q96QB1-2

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78115

AN:

151826

Hom.:

20483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.479

GnomAD3 exomes

AF:

0.484

AC:

121025

AN:

250248

Hom.:

30271

AF XY:

0.495

AC XY:

66949

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.609

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.534

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.493

GnomAD4 exome

AF:

0.493

AC:

720068

AN:

1460434

Hom.:

180094

Cov.:

AF XY:

0.497

AC XY:

360904

AN XY:

726618

show subpopulations

Gnomad4 AFR exome

AF:

0.614

Gnomad4 AMR exome

AF:

0.330

Gnomad4 ASJ exome

AF:

0.528

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.604

Gnomad4 FIN exome

AF:

0.464

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.515

AC:

78187

AN:

151944

Hom.:

20515

Cov.:

AF XY:

0.514

AC XY:

38190

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.535

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.495

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.495

Hom.:

44880

Bravo

AF:

0.509

TwinsUK

AF:

0.490

AC:

1818

ALSPAC

AF:

0.474

AC:

1827

ESP6500AA

AF:

0.589

AC:

2595

ESP6500EA

AF:

0.493

AC:

4236

ExAC

AF:

0.493

AC:

59896

Asia WGS

AF:

0.471

AC:

1638

AN:

3478

EpiCase

AF:

0.494

EpiControl

AF:

0.502

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.14

DANN

Benign

0.86

DEOGEN2

Benign

0.036

T;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.23

T;T;T;T

MetaRNN

Benign

0.000011

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.11

N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

0.55

N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.087

MPC

0.023

ClinPred

0.0081

GERP RS

-6.1

Varity_R

0.030

gMVP

0.22

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