8-13085576-AT-A

Position:

• chr8-13085576-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_182643.3(DLC1):​c.*234del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 314,530 control chromosomes in the GnomAD database, including 404 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (386 hom., cov: 31)
  • Exomes 𝑓: 0.17 (18 hom.)
• Consequence: DLC1 NM_182643.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.575

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-13085576-AT-A is Benign according to our data. Variant chr8-13085576-AT-A is described in ClinVar as [Benign]. Clinvar id is 1234529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.*234del		3_prime_UTR_variant	18/18	ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.*234del		3_prime_UTR_variant	18/18	1	NM_182643.3

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 9948 AN: 144098 Hom.: 385 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.00199

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.0752

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0634

GnomAD4 exome AF: 0.174 AC: 29714 AN: 170378 Hom.: 18 Cov.: 0 AF XY: 0.175 AC XY: 15270 AN XY: 87014

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.0921

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.0691 AC: 9967 AN: 144152 Hom.: 386 Cov.: 31 AF XY: 0.0679 AC XY: 4760 AN XY: 70056

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.00219

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0621

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs60094700; hg19: chr8-12943085;