chr8-13403027-C-T

Position:

• chr8-13403027-C-T

Variant summary

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

The NM_182643.3(DLC1):​c.1024-1408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,238 control chromosomes in the GnomAD database, including 54,638 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 0.85 (54638 hom., cov: 33)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.1024-1408G>A		intron_variant		ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.1024-1408G>A		intron_variant		1	NM_182643.3
DLC1	ENST00000511869.1	c.1024-1408G>A		intron_variant		1
DLC1	ENST00000316609.9	c.1024-1408G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128764 AN: 152120 Hom.: 54603 Cov.: 33

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.846 AC: 128849 AN: 152238 Hom.: 54638 Cov.: 33 AF XY: 0.847 AC XY: 63028 AN XY: 74432

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.855

Alfa AF: 0.842 Hom.: 107474

Bravo AF: 0.855

Asia WGS AF: 0.866 AC: 3009 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.062
DANN	Benign	0.77

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: rs289585; hg19: chr8-13260536;