chr8-13201165-C-G

Variant names:

• chr8-13201165-C-G
• rs2016444
• NM_182643.3:c.1349-85508G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182643.3(DLC1):​c.1349-85508G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 150,932 control chromosomes in the GnomAD database, including 1,749 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 0.11 (1749 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864
• Publications: 6 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

ENSG00000287134 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1349-85508G>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.1349-85508G>C		intron_variant	Intron 5 of 17	1	NM_182643.3	ENSP00000276297.4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16392 AN: 150840 Hom.: 1745 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.109 AC: 16420 AN: 150932 Hom.: 1749 Cov.: 32 AF XY: 0.113 AC XY: 8285 AN XY: 73636

African (AFR) AF: 0.237 AC: 9784 AN: 41236

American (AMR) AF: 0.183 AC: 2778 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3464

East Asian (EAS) AF: 0.311 AC: 1595 AN: 5136

South Asian (SAS) AF: 0.0711 AC: 340 AN: 4784

European-Finnish (FIN) AF: 0.0485 AC: 487 AN: 10044

Middle Eastern (MID) AF: 0.0319 AC: 9 AN: 282

European-Non Finnish (NFE) AF: 0.0172 AC: 1163 AN: 67796

Other (OTH) AF: 0.0916 AC: 191 AN: 2086

Alfa AF: 0.0637 Hom.: 115

Bravo AF: 0.126

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.86
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: rs2016444; hg19: chr8-13058674;