NM_182643.3:c.1349-7481A>C

Variant names:

• chr8-13123138-T-G
• rs9325866
• NM_182643.3:c.1349-7481A>C

Variant summary

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

The NM_182643.3(DLC1):​c.1349-7481A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,946 control chromosomes in the GnomAD database, including 15,052 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 0.41 (15052 hom., cov: 31)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1349-7481A>C		intron_variant	Intron 5 of 17	ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.1349-7481A>C		intron_variant	Intron 5 of 17	1	NM_182643.3	ENSP00000276297.4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62389 AN: 151828 Hom.: 15025 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.411 AC: 62477 AN: 151946 Hom.: 15052 Cov.: 31 AF XY: 0.409 AC XY: 30368 AN XY: 74278

African (AFR) AF: 0.664 AC: 27495 AN: 41422

American (AMR) AF: 0.418 AC: 6380 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1590 AN: 5138

South Asian (SAS) AF: 0.456 AC: 2192 AN: 4810

European-Finnish (FIN) AF: 0.243 AC: 2571 AN: 10584

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19764 AN: 67944

Other (OTH) AF: 0.388 AC: 819 AN: 2110

Alfa AF: 0.341 Hom.: 18586

Bravo AF: 0.436

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.51
PhyloP100		0.15
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: rs9325866; hg19: chr8-12980647;