rs3816748

chr8-13499831-G-C

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.241C>G(p.Leu81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,030 control chromosomes in the GnomAD database, including 2,550 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 0.034 (311 hom., cov: 33)
  • Exomes 𝑓: 0.026 (2239 hom.)
• Consequence: DLC1 NM_182643.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15

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=0.001494199).
• BP6: Variant 8-13499831-G-C is Benign according to our data. Variant chr8-13499831-G-C is described in ClinVar as [Benign]. Clinvar id is 1600976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.241C>G	p.Leu81Val	missense_variant	2/18	ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.241C>G	p.Leu81Val	missense_variant	2/18	1	NM_182643.3

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5123 AN: 152144 Hom.: 310 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00853

Gnomad OTH AF: 0.0345

GnomAD3 exomes AF: 0.0617 AC: 15517 AN: 251324 Hom.: 1315 AF XY: 0.0569 AC XY: 7735 AN XY: 135840

Gnomad AFR exome AF: 0.0197

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.00625

Gnomad EAS exome AF: 0.232

Gnomad SAS exome AF: 0.0886

Gnomad FIN exome AF: 0.0282

Gnomad NFE exome AF: 0.00883

Gnomad OTH exome AF: 0.0398

GnomAD4 exome AF: 0.0258 AC: 37663 AN: 1461768 Hom.: 2239 Cov.: 55 AF XY: 0.0266 AC XY: 19337 AN XY: 727194

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.00677

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.0871

Gnomad4 FIN exome AF: 0.0278

Gnomad4 NFE exome AF: 0.00896

Gnomad4 OTH exome AF: 0.0316

GnomAD4 genome AF: 0.0337 AC: 5126 AN: 152262 Hom.: 311 Cov.: 33 AF XY: 0.0373 AC XY: 2780 AN XY: 74458

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.00853

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0173 Hom.: 106

Bravo AF: 0.0398

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.0195 AC: 86

ESP6500EA AF: 0.00895 AC: 77

ExAC AF: 0.0560 AC: 6804

Asia WGS AF: 0.138 AC: 477 AN: 3476

EpiCase AF: 0.00703

EpiControl AF: 0.00616

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	0.057
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.053
Dann	Benign	0.097
DEOGEN2	Benign	0.029	T;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.52	T;.;.;.
MetaRNN	Benign	0.0015	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.90	N;N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.17	N;N;N;.
REVEL	Benign	0.018
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.75	T;T;T;.
Polyphen		0.0	B;B;.;.
Vest4		0.043
MPC		0.023
ClinPred		0.0093	T
GERP RS		-5.5
Varity_R		0.032
gMVP		0.024

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: rs3816748; hg19: chr8-13357340; COSMIC: COSV52295645; COSMIC: COSV52295645;