8-13290712-T-G

Variant names:

• chr8-13290712-T-G
• rs3842964
• NM_182643.3:c.1348+14557A>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.1348+14557A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,994 control chromosomes in the GnomAD database, including 8,438 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 0.32 (8438 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1348+14557A>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.1348+14557A>C		intron_variant	Intron 5 of 17	1	NM_182643.3	ENSP00000276297.4
DLC1	ENST00000316609.9	c.1348+14557A>C		intron_variant	Intron 5 of 5	2		ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48620 AN: 151876 Hom.: 8440 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.320 AC: 48627 AN: 151994 Hom.: 8438 Cov.: 32 AF XY: 0.313 AC XY: 23279 AN XY: 74292

African (AFR) AF: 0.223 AC: 9244 AN: 41434

American (AMR) AF: 0.379 AC: 5781 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3470

East Asian (EAS) AF: 0.0736 AC: 381 AN: 5176

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4814

European-Finnish (FIN) AF: 0.306 AC: 3231 AN: 10562

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26152 AN: 67954

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.363 Hom.: 38353

Bravo AF: 0.326

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		2.3
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: rs3842964; hg19: chr8-13148221;