8-13086182-C-T

Position:

• chr8-13086182-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182643.3(DLC1):​c.4466+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,439,722 control chromosomes in the GnomAD database, including 189,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20587 hom., cov: 33)
  • Exomes 𝑓: 0.51 (168674 hom.)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.800

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-13086182-C-T is Benign according to our data. Variant chr8-13086182-C-T is described in ClinVar as [Benign]. Clinvar id is 1222600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.4466+108G>A		intron_variant		ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.4466+108G>A		intron_variant		1	NM_182643.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78664 AN: 151932 Hom.: 20564 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.509 AC: 655134 AN: 1287672 Hom.: 168674 Cov.: 20 AF XY: 0.512 AC XY: 324579 AN XY: 633468

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.509

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.518 AC: 78729 AN: 152050 Hom.: 20587 Cov.: 33 AF XY: 0.518 AC XY: 38517 AN XY: 74320

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.496

Alfa AF: 0.502 Hom.: 4735

Bravo AF: 0.510

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.69

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: rs621554; hg19: chr8-12943691;