8-13086116-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182643.3(DLC1):c.4466+174G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,320,198 control chromosomes in the GnomAD database, including 1,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (278 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1119 hom.)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.486

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-13086116-C-G is Benign according to our data. Variant chr8-13086116-C-G is described in ClinVar as [Benign]. Clinvar id is 1234582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.4466+174G>C		intron_variant		ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.4466+174G>C		intron_variant		1	NM_182643.3

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8099 AN: 152162 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0410 AC: 47919 AN: 1167918 Hom.: 1119 Cov.: 17 AF XY: 0.0412 AC XY: 23582 AN XY: 572746

Gnomad4 AFR exome AF: 0.0973

Gnomad4 AMR exome AF: 0.0242

Gnomad4 ASJ exome AF: 0.0860

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0378

Gnomad4 FIN exome AF: 0.0361

Gnomad4 NFE exome AF: 0.0406

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0533 AC: 8115 AN: 152280 Hom.: 278 Cov.: 32 AF XY: 0.0525 AC XY: 3908 AN XY: 74464

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0174 Hom.: 9

Bravo AF: 0.0548

Asia WGS AF: 0.0210 AC: 75 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.0
Dann	Benign	0.44

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: rs61430919; hg19: chr8-12943625;