8-13598622-G-T

Variant names:

• chr8-13598622-G-T
• rs1021087
• NM_001348081.2:c.-126+5915C>A

Variant summary

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

The NM_001348081.2(DLC1):​c.-126+5915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 151,980 control chromosomes in the GnomAD database, including 47,793 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 0.79 (47793 hom., cov: 32)
• Consequence: DLC1 NM_001348081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_001348081.2	c.-126+5915C>A		intron_variant	Intron 1 of 17		NP_001335010.1
DLC1	NM_001348082.2	c.-1577+5915C>A		intron_variant	Intron 1 of 16		NP_001335011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000631382.1	c.-126+5915C>A		intron_variant	Intron 1 of 1	2		ENSP00000488100.1
DLC1	ENST00000529018.1	n.74+5915C>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119990 AN: 151860 Hom.: 47736 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.790 AC: 120110 AN: 151980 Hom.: 47793 Cov.: 32 AF XY: 0.790 AC XY: 58655 AN XY: 74282

African (AFR) AF: 0.873 AC: 36241 AN: 41510

American (AMR) AF: 0.763 AC: 11618 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2903 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4491 AN: 5158

South Asian (SAS) AF: 0.891 AC: 4300 AN: 4826

European-Finnish (FIN) AF: 0.670 AC: 7064 AN: 10550

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51077 AN: 67918

Other (OTH) AF: 0.800 AC: 1689 AN: 2110

Alfa AF: 0.774 Hom.: 94456

Bravo AF: 0.799

Asia WGS AF: 0.893 AC: 3101 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.35
DANN	Benign	0.40
PhyloP100		-0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1021087; hg19: chr8-13456131;