8-13331883-A-T

Position:

• chr8-13331883-A-T

Variant summary

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

The NM_182643.3(DLC1):​c.1315-26581T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,172 control chromosomes in the GnomAD database, including 56,170 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 0.86 (56170 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1315-26581T>A		intron_variant		ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.1315-26581T>A		intron_variant		1	NM_182643.3	ENSP00000276297.4
DLC1	ENST00000511869.1	c.1315-26581T>A		intron_variant		1		ENSP00000425878.1
DLC1	ENST00000316609.9	c.1315-26581T>A		intron_variant		2		ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130180 AN: 152054 Hom.: 56139 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.856 AC: 130261 AN: 152172 Hom.: 56170 Cov.: 32 AF XY: 0.857 AC XY: 63726 AN XY: 74388

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.929

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.876

Alfa AF: 0.868 Hom.: 7140

Bravo AF: 0.857

Asia WGS AF: 0.898 AC: 3125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.48

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: rs1454947; hg19: chr8-13189392;