8-13598622-G-T

Variant names:

• chr8-13598622-G-T
• rs1021087
• NM_001348081.2:c.-126+5915C>A

Variant summary

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

The NM_001348081.2(DLC1):​c.-126+5915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 151,980 control chromosomes in the GnomAD database, including 47,793 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 0.79 (47793 hom., cov: 32)
• Consequence: DLC1 NM_001348081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_001348081.2	c.-126+5915C>A		intron_variant	Intron 1 of 17		NP_001335010.1
DLC1	NM_001348082.2	c.-1577+5915C>A		intron_variant	Intron 1 of 16		NP_001335011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000631382.1	c.-126+5915C>A		intron_variant	Intron 1 of 1	2		ENSP00000488100.1
DLC1	ENST00000529018.1	n.74+5915C>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119990 AN: 151860 Hom.: 47736 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.790 AC: 120110 AN: 151980 Hom.: 47793 Cov.: 32 AF XY: 0.790 AC XY: 58655 AN XY: 74282

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.800

Alfa AF: 0.767 Hom.: 61223

Bravo AF: 0.799

Asia WGS AF: 0.893 AC: 3101 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.35
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1021087; hg19: chr8-13456131;