8-13129297-T-C

Variant names:

• chr8-13129297-T-C
• rs35335364
• NM_182643.3:c.1349-13640A>G

Variant summary

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

The NM_182643.3(DLC1):​c.1349-13640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,246 control chromosomes in the GnomAD database, including 1,667 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 0.14 (1667 hom., cov: 33)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1349-13640A>G		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.1349-13640A>G		intron_variant	Intron 5 of 17	1	NM_182643.3	ENSP00000276297.4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21408 AN: 152128 Hom.: 1663 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.141 AC: 21431 AN: 152246 Hom.: 1667 Cov.: 33 AF XY: 0.141 AC XY: 10528 AN XY: 74440

African (AFR) AF: 0.119 AC: 4945 AN: 41540

American (AMR) AF: 0.0944 AC: 1444 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.0369 AC: 191 AN: 5182

South Asian (SAS) AF: 0.149 AC: 718 AN: 4828

European-Finnish (FIN) AF: 0.234 AC: 2483 AN: 10598

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10745 AN: 68010

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.140 Hom.: 2408

Bravo AF: 0.129

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-1.0
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: rs35335364; hg19: chr8-12986806;