8-13403027-C-T

Variant names:

• chr8-13403027-C-T
• rs289585
• NM_182643.3:c.1024-1408G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182643.3(DLC1):​c.1024-1408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,238 control chromosomes in the GnomAD database, including 54,638 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 0.85 (54638 hom., cov: 33)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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.1024-1408G>A		intron	N/A	NP_872584.2
	DLC1	NM_001348081.2		c.1024-1408G>A		intron	N/A	NP_001335010.1
	DLC1	NM_001413124.1		c.1024-1408G>A		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.1024-1408G>A		intron	N/A	ENSP00000276297.4
	DLC1	ENST00000511869.1	TSL:1	c.1024-1408G>A		intron	N/A	ENSP00000425878.1
	DLC1	ENST00000316609.9	TSL:2	c.1024-1408G>A		intron	N/A	ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128764 AN: 152120 Hom.: 54603 Cov.: 33

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.846 AC: 128849 AN: 152238 Hom.: 54638 Cov.: 33 AF XY: 0.847 AC XY: 63028 AN XY: 74432

African (AFR) AF: 0.841 AC: 34931 AN: 41536

American (AMR) AF: 0.879 AC: 13444 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2960 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5058 AN: 5180

South Asian (SAS) AF: 0.808 AC: 3901 AN: 4828

European-Finnish (FIN) AF: 0.834 AC: 8836 AN: 10596

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 57003 AN: 68014

Other (OTH) AF: 0.855 AC: 1807 AN: 2114

Alfa AF: 0.844 Hom.: 225187

Bravo AF: 0.855

Asia WGS AF: 0.866 AC: 3009 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.062
DANN	Benign	0.77
PhyloP100		-1.5
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: rs289585; hg19: chr8-13260536;