8-13481859-G-A

Variant names:

• chr8-13481859-G-A
• rs1481692
• NM_182643.3:c.1023+17190C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182643.3(DLC1):​c.1023+17190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,084 control chromosomes in the GnomAD database, including 44,784 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 0.76 (44784 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182643.3. 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_182643.3	MANE Select	c.1023+17190C>T		intron	N/A	NP_872584.2
	DLC1	NM_001348081.2		c.1023+17190C>T		intron	N/A	NP_001335010.1
	DLC1	NM_001413124.1		c.1023+17190C>T		intron	N/A	NP_001400053.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	ENST00000276297.9	TSL:1 MANE Select	c.1023+17190C>T		intron	N/A	ENSP00000276297.4
	DLC1	ENST00000511869.1	TSL:1	c.1023+17190C>T		intron	N/A	ENSP00000425878.1
	DLC1	ENST00000316609.9	TSL:2	c.1023+17190C>T		intron	N/A	ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114809 AN: 151964 Hom.: 44760 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.755 AC: 114880 AN: 152084 Hom.: 44784 Cov.: 32 AF XY: 0.746 AC XY: 55436 AN XY: 74338

African (AFR) AF: 0.655 AC: 27140 AN: 41458

American (AMR) AF: 0.627 AC: 9576 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2994 AN: 3470

East Asian (EAS) AF: 0.374 AC: 1933 AN: 5162

South Asian (SAS) AF: 0.679 AC: 3267 AN: 4812

European-Finnish (FIN) AF: 0.787 AC: 8324 AN: 10574

Middle Eastern (MID) AF: 0.887 AC: 259 AN: 292

European-Non Finnish (NFE) AF: 0.866 AC: 58888 AN: 68022

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.833 Hom.: 73147

Bravo AF: 0.737

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.75
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1481692; hg19: chr8-13339368;