rs561681

Variant names:

• chr8-13093516-A-G
• rs561681
• NM_182643.3:c.3527-691T>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.3527-691T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,028 control chromosomes in the GnomAD database, including 25,228 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 0.57 (25228 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 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.3527-691T>C		intron	N/A	NP_872584.2	Q96QB1-2
	DLC1	NM_001348081.2		c.3527-691T>C		intron	N/A	NP_001335010.1	Q96QB1-2
	DLC1	NM_001413124.1		c.3527-691T>C		intron	N/A	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.3527-691T>C		intron	N/A	ENSP00000276297.4	Q96QB1-2
	DLC1	ENST00000358919.6	TSL:1	c.2216-691T>C		intron	N/A	ENSP00000351797.2	Q96QB1-1
	DLC1	ENST00000941272.1		c.3527-691T>C		intron	N/A	ENSP00000611331.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86726 AN: 151910 Hom.: 25195 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.571 AC: 86807 AN: 152028 Hom.: 25228 Cov.: 32 AF XY: 0.572 AC XY: 42523 AN XY: 74308

African (AFR) AF: 0.650 AC: 26956 AN: 41482

American (AMR) AF: 0.469 AC: 7165 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2166 AN: 3470

East Asian (EAS) AF: 0.374 AC: 1938 AN: 5184

South Asian (SAS) AF: 0.658 AC: 3167 AN: 4816

European-Finnish (FIN) AF: 0.545 AC: 5753 AN: 10548

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37996 AN: 67960

Other (OTH) AF: 0.532 AC: 1116 AN: 2096

Alfa AF: 0.565 Hom.: 14516

Bravo AF: 0.560

Asia WGS AF: 0.502 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.66
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: rs561681; hg19: chr8-12951025;