rs289519

Variant names:

• chr8-13379539-T-C
• rs289519
• NM_182643.3:c.1314+14014A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-13379539-T-C
• chr8-13379539-T-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.1314+14014A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,104 control chromosomes in the GnomAD database, including 34,097 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 0.66 (34097 hom., cov: 33)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	NM_182643.3	MANE Select	c.1314+14014A>G		intron	N/A	NP_872584.2
	DLC1	NM_001348081.2		c.1314+14014A>G		intron	N/A	NP_001335010.1
	DLC1	NM_001413124.1		c.1314+14014A>G		intron	N/A	NP_001400053.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	ENST00000276297.9	TSL:1 MANE Select	c.1314+14014A>G		intron	N/A	ENSP00000276297.4
	DLC1	ENST00000511869.1	TSL:1	c.1314+14014A>G		intron	N/A	ENSP00000425878.1
	DLC1	ENST00000316609.9	TSL:2	c.1314+14014A>G		intron	N/A	ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101002 AN: 151986 Hom.: 34055 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.665 AC: 101104 AN: 152104 Hom.: 34097 Cov.: 33 AF XY: 0.662 AC XY: 49246 AN XY: 74352

African (AFR) AF: 0.753 AC: 31267 AN: 41508

American (AMR) AF: 0.626 AC: 9567 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4342 AN: 5172

South Asian (SAS) AF: 0.571 AC: 2756 AN: 4828

European-Finnish (FIN) AF: 0.585 AC: 6178 AN: 10558

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.626 AC: 42566 AN: 67976

Other (OTH) AF: 0.642 AC: 1354 AN: 2110

Alfa AF: 0.580 Hom.: 2509

Bravo AF: 0.674

Asia WGS AF: 0.704 AC: 2448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		-1.8
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: rs289519; hg19: chr8-13237048;