rs11785331

Variant names:

• chr8-13577412-T-C
• rs11785331
• NM_001348081.2:c.-126+27125A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

DLC1 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348081.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	NM_001348081.2		c.-126+27125A>G		intron	N/A	NP_001335010.1
	DLC1	NM_001348082.2		c.-1577+27125A>G		intron	N/A	NP_001335011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	ENST00000631382.1	TSL:2	c.-126+27125A>G		intron	N/A	ENSP00000488100.1
	DLC1	ENST00000529018.1	TSL:5	n.75-18024A>G		intron	N/A

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

African (AFR) AF: 0.131 AC: 5434 AN: 41490

American (AMR) AF: 0.0883 AC: 1350 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3472

East Asian (EAS) AF: 0.0588 AC: 304 AN: 5174

South Asian (SAS) AF: 0.176 AC: 847 AN: 4820

European-Finnish (FIN) AF: 0.0362 AC: 384 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0725 AC: 4933 AN: 67998

Other (OTH) AF: 0.105 AC: 222 AN: 2114

Alfa AF: 0.0859 Hom.: 735

Bravo AF: 0.0944

Asia WGS AF: 0.126 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.76
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs11785331; hg19: chr8-13434921;