rs3988457

Positions:

• chr8-13491344-C-A

Variant summary

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

The NM_182643.3(DLC1):​c.1023+7705G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 151,802 control chromosomes in the GnomAD database, including 44,392 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 0.75 (44392 hom., cov: 29)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.1023+7705G>T		intron_variant		ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.1023+7705G>T		intron_variant		1	NM_182643.3
DLC1	ENST00000511869.1	c.1023+7705G>T		intron_variant		1
DLC1	ENST00000316609.9	c.1023+7705G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114159 AN: 151684 Hom.: 44367 Cov.: 29

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.752 AC: 114231 AN: 151802 Hom.: 44392 Cov.: 29 AF XY: 0.742 AC XY: 55079 AN XY: 74212

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.767

Alfa AF: 0.830 Hom.: 24103

Bravo AF: 0.733

Asia WGS AF: 0.580 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.64

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: rs3988457; hg19: chr8-13348853;