rs3842964

Variant names:

• chr8-13290712-T-A
• rs3842964
• NM_182643.3:c.1348+14557A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-13290712-T-A
• chr8-13290712-T-C
• chr8-13290712-T-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_182643.3(DLC1):​c.1348+14557A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 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: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 5 AD,Unknown gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151956 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74338

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 38353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		2.3

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;