8-13123138-T-G

Position:

• chr8-13123138-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182643.3(DLC1):​c.1349-7481A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,946 control chromosomes in the GnomAD database, including 15,052 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (15052 hom., cov: 31)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1349-7481A>C		intron_variant		ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.1349-7481A>C		intron_variant		1	NM_182643.3	ENSP00000276297

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62389 AN: 151828 Hom.: 15025 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62477 AN: 151946 Hom.: 15052 Cov.: 31 AF XY: 0.409 AC XY: 30368 AN XY: 74278

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.388

Alfa AF: 0.328 Hom.: 12376

Bravo AF: 0.436

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.51

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: rs9325866; hg19: chr8-12980647;