rs609020

chr8-13091442-A-Gchr8-13091442-A-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.3741-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,609,414 control chromosomes in the GnomAD database, including 254,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27235 hom., cov: 31)
  • Exomes 𝑓: 0.55 (227600 hom.)
• Consequence: DLC1 NM_182643.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001604
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.44

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 (BayesDel_noAF=-0.7).
• BP6: Variant 8-13091442-A-G is Benign according to our data. Variant chr8-13091442-A-G is described in ClinVar as [Benign]. Clinvar id is 1600292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.3741-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.3741-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_182643.3

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89744 AN: 151804 Hom.: 27204 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.548

GnomAD3 exomes AF: 0.545 AC: 136500 AN: 250642 Hom.: 38576 AF XY: 0.555 AC XY: 75143 AN XY: 135514

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.401

Gnomad SAS exome AF: 0.656

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.560

Gnomad OTH exome AF: 0.557

GnomAD4 exome AF: 0.555 AC: 808818 AN: 1457492 Hom.: 227600 Cov.: 30 AF XY: 0.559 AC XY: 405124 AN XY: 725242

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.591 AC: 89824 AN: 151922 Hom.: 27235 Cov.: 31 AF XY: 0.592 AC XY: 43969 AN XY: 74286

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.547

Alfa AF: 0.566 Hom.: 14127

Bravo AF: 0.584

Asia WGS AF: 0.510 AC: 1777 AN: 3478

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
BayesDel_noAF	Benign	-0.70
Cadd	Benign	9.5
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.034
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: rs609020; hg19: chr8-12948951; COSMIC: COSV52288544; COSMIC: COSV52288544;