rs2016444

chr8-13201165-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182643.3(DLC1):c.1349-85508G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 150,932 control chromosomes in the GnomAD database, including 1,749 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 0.11 (1749 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.1349-85508G>C		intron_variant		ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.1349-85508G>C		intron_variant		1	NM_182643.3
	ENST00000662638.1	n.262-2061C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16392 AN: 150840 Hom.: 1745 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.109 AC: 16420 AN: 150932 Hom.: 1749 Cov.: 32 AF XY: 0.113 AC XY: 8285 AN XY: 73636

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0916

Alfa AF: 0.0637 Hom.: 115

Bravo AF: 0.126

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	16
Dann	Benign	0.85

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: rs2016444; hg19: chr8-13058674;