rs3739298

Variant names:

• chr8-13100516-C-A
• rs3739298
• NM_182643.3:c.1821G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-13100516-C-A
• chr8-13100516-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182643.3(DLC1):​c.1821G>T​(p.Ala607Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,611,792 control chromosomes in the GnomAD database, including 99,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7898 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92002 hom.)
• Consequence: DLC1 NM_182643.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.02
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-13100516-C-A is Benign according to our data. Variant chr8-13100516-C-A is described in ClinVar as Benign. ClinVar VariationId is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182643.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	NM_182643.3	MANE Select	c.1821G>T	p.Ala607Ala	synonymous	Exon 9 of 18	NP_872584.2	Q96QB1-2
	DLC1	NM_001348081.2		c.1821G>T	p.Ala607Ala	synonymous	Exon 9 of 18	NP_001335010.1	Q96QB1-2
	DLC1	NM_001413124.1		c.1821G>T	p.Ala607Ala	synonymous	Exon 9 of 18	NP_001400053.1	Q96QB1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	ENST00000276297.9	TSL:1 MANE Select	c.1821G>T	p.Ala607Ala	synonymous	Exon 9 of 18	ENSP00000276297.4	Q96QB1-2
	DLC1	ENST00000358919.6	TSL:1	c.510G>T	p.Ala170Ala	synonymous	Exon 5 of 14	ENSP00000351797.2	Q96QB1-1
	DLC1	ENST00000941272.1		c.1821G>T	p.Ala607Ala	synonymous	Exon 10 of 19	ENSP00000611331.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45778 AN: 151660 Hom.: 7885 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.347

GnomAD2 exomes AF: 0.372 AC: 92134 AN: 248004 AF XY: 0.361

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.347 AC: 506127 AN: 1460014 Hom.: 92002 Cov.: 82 AF XY: 0.344 AC XY: 250066 AN XY: 726394

African (AFR) AF: 0.145 AC: 4851 AN: 33478

American (AMR) AF: 0.574 AC: 25655 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7143 AN: 26134

East Asian (EAS) AF: 0.593 AC: 23549 AN: 39700

South Asian (SAS) AF: 0.295 AC: 25408 AN: 86254

European-Finnish (FIN) AF: 0.355 AC: 18347 AN: 51704

Middle Eastern (MID) AF: 0.224 AC: 1287 AN: 5756

European-Non Finnish (NFE) AF: 0.341 AC: 379307 AN: 1111902

Other (OTH) AF: 0.341 AC: 20580 AN: 60370

GnomAD4 genome AF: 0.302 AC: 45799 AN: 151778 Hom.: 7898 Cov.: 32 AF XY: 0.301 AC XY: 22345 AN XY: 74180

African (AFR) AF: 0.155 AC: 6417 AN: 41414

American (AMR) AF: 0.439 AC: 6699 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3003 AN: 5116

South Asian (SAS) AF: 0.297 AC: 1428 AN: 4804

European-Finnish (FIN) AF: 0.353 AC: 3716 AN: 10526

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22557 AN: 67884

Other (OTH) AF: 0.350 AC: 738 AN: 2106

Alfa AF: 0.315 Hom.: 2419

Bravo AF: 0.312

Asia WGS AF: 0.454 AC: 1577 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.330

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.6
DANN	Benign	0.62
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: rs3739298; hg19: chr8-12958025; COSMIC: COSV52288914; COSMIC: COSV52288914;