8-13091442-A-G

Variant names:

• chr8-13091442-A-G
• rs609020
• NM_182643.3:c.3741-10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182643.3(DLC1):​c.3741-10T>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.0001604
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.44
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1600292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.3741-10T>C		intron_variant	Intron 13 of 17	ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.3741-10T>C		intron_variant	Intron 13 of 17	1	NM_182643.3	ENSP00000276297.4

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

GnomAD2 exomes AF: 0.545 AC: 136500 AN: 250642 AF XY: 0.555

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 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

African (AFR) AF: 0.726 AC: 24225 AN: 33346

American (AMR) AF: 0.371 AC: 16525 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 16153 AN: 26064

East Asian (EAS) AF: 0.369 AC: 14632 AN: 39666

South Asian (SAS) AF: 0.657 AC: 56442 AN: 85948

European-Finnish (FIN) AF: 0.542 AC: 28927 AN: 53352

Middle Eastern (MID) AF: 0.649 AC: 3728 AN: 5746

European-Non Finnish (NFE) AF: 0.554 AC: 614090 AN: 1108616

Other (OTH) AF: 0.566 AC: 34096 AN: 60224

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

African (AFR) AF: 0.718 AC: 29725 AN: 41422

American (AMR) AF: 0.478 AC: 7297 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1977 AN: 5144

South Asian (SAS) AF: 0.663 AC: 3185 AN: 4806

European-Finnish (FIN) AF: 0.545 AC: 5754 AN: 10558

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38020 AN: 67942

Other (OTH) AF: 0.547 AC: 1155 AN: 2110

Alfa AF: 0.566 Hom.: 15355

Bravo AF: 0.584

Asia WGS AF: 0.510 AC: 1777 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.5
DANN	Benign	0.83
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs609020; hg19: chr8-12948951; COSMIC: COSV52288544; COSMIC: COSV52288544;