rs3988460

Variant names:

• chr8-13306705-G-A
• rs3988460
• NM_182643.3:c.1315-1403C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182643.3(DLC1):​c.1315-1403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,650 control chromosomes in the GnomAD database, including 11,253 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 0.37 (11253 hom., cov: 29)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 3 publications found

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]

DLC1 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1315-1403C>T		intron_variant	Intron 4 of 17	ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.1315-1403C>T		intron_variant	Intron 4 of 17	1	NM_182643.3	ENSP00000276297.4
DLC1	ENST00000511869.1	c.1315-1403C>T		intron_variant	Intron 4 of 4	1		ENSP00000425878.1
DLC1	ENST00000316609.9	c.1315-1403C>T		intron_variant	Intron 4 of 5	2		ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56638 AN: 151532 Hom.: 11259 Cov.: 29

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.374 AC: 56654 AN: 151650 Hom.: 11253 Cov.: 29 AF XY: 0.368 AC XY: 27232 AN XY: 74090

African (AFR) AF: 0.265 AC: 10947 AN: 41318

American (AMR) AF: 0.450 AC: 6853 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3468

East Asian (EAS) AF: 0.117 AC: 604 AN: 5144

South Asian (SAS) AF: 0.387 AC: 1856 AN: 4796

European-Finnish (FIN) AF: 0.327 AC: 3438 AN: 10514

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29922 AN: 67878

Other (OTH) AF: 0.398 AC: 838 AN: 2108

Alfa AF: 0.420 Hom.: 7130

Bravo AF: 0.380

Asia WGS AF: 0.273 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3988460; hg19: chr8-13164214;