rs532841

chr8-13099966-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182643.3(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 NM_182643.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.564

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
DLC1	NM_182643.3	c.2371G>A	p.Val791Met	missense_variant	9/18	ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.2371G>A	p.Val791Met	missense_variant	9/18	1	NM_182643.3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78115 AN: 151826 Hom.: 20483 Cov.: 32

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

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.: 83 AF XY: 0.497 AC XY: 360904 AN XY: 726618

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.: 32 AF XY: 0.514 AC XY: 38190 AN XY: 74244

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.77	T
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	N
LIST_S2	Benign	0.23	T;T;T;T
MetaRNN	Benign	0.000011	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.11	N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs532841; hg19: chr8-12957475; COSMIC: COSV52288554; COSMIC: COSV52288554;