rs2278945

chr8-13341642-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182643.3(DLC1):c.1315-36340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,934 control chromosomes in the GnomAD database, including 18,573 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 0.49 (18572 hom., cov: 31)
  • Exomes 𝑓: 0.32 (1 hom.)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.1315-36340G>A		intron_variant		ENST00000276297.9
LOC101930149	XR_007060830.1	n.460+2152C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.1315-36340G>A		intron_variant		1	NM_182643.3
DLC1	ENST00000511869.1	c.1315-36340G>A		intron_variant		1
	ENST00000523495.1	n.2376C>T		non_coding_transcript_exon_variant	2/2	5
DLC1	ENST00000316609.9	c.1315-36340G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73965 AN: 151794 Hom.: 18573 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.318 AC: 7 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.278

GnomAD4 genome AF: 0.487 AC: 73993 AN: 151912 Hom.: 18572 Cov.: 31 AF XY: 0.494 AC XY: 36655 AN XY: 74262

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.499

Alfa AF: 0.508 Hom.: 15726

Bravo AF: 0.482

Asia WGS AF: 0.498 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.11
Dann	Benign	0.81

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: rs2278945; hg19: chr8-13199151;