rs11785331

Positions:

• chr8-13577412-T-C

Variant summary

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

The NM_001348081.2(DLC1):​c.-126+27125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,170 control chromosomes in the GnomAD database, including 777 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 0.092 (777 hom., cov: 32)
• Consequence: DLC1 NM_001348081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLC1	NM_001348081.2	c.-126+27125A>G		intron_variant			NP_001335010.1
DLC1	NM_001348082.2	c.-1577+27125A>G		intron_variant			NP_001335011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000631382.1	c.-126+27125A>G		intron_variant		2		ENSP00000488100
DLC1	ENST00000529018.1	n.75-18024A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14030 AN: 152052 Hom.: 775 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0726

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0924 AC: 14054 AN: 152170 Hom.: 777 Cov.: 32 AF XY: 0.0927 AC XY: 6897 AN XY: 74388

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0588

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.0362

Gnomad4 NFE AF: 0.0725

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0841 Hom.: 557

Bravo AF: 0.0944

Asia WGS AF: 0.126 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11785331; hg19: chr8-13434921;