rs3988457

Variant names:

• chr8-13491344-C-A
• rs3988457
• NM_182643.3:c.1023+7705G>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.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
• Publications: 2 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=-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 rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1023+7705G>T		intron_variant	Intron 2 of 17	ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.1023+7705G>T		intron_variant	Intron 2 of 17	1	NM_182643.3	ENSP00000276297.4
DLC1	ENST00000511869.1	c.1023+7705G>T		intron_variant	Intron 2 of 4	1		ENSP00000425878.1
DLC1	ENST00000316609.9	c.1023+7705G>T		intron_variant	Intron 2 of 5	2		ENSP00000321034.5

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

African (AFR) AF: 0.648 AC: 26833 AN: 41388

American (AMR) AF: 0.625 AC: 9521 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2991 AN: 3468

East Asian (EAS) AF: 0.374 AC: 1922 AN: 5140

South Asian (SAS) AF: 0.660 AC: 3179 AN: 4816

European-Finnish (FIN) AF: 0.787 AC: 8262 AN: 10504

Middle Eastern (MID) AF: 0.901 AC: 263 AN: 292

European-Non Finnish (NFE) AF: 0.865 AC: 58784 AN: 67944

Other (OTH) AF: 0.767 AC: 1616 AN: 2106

Alfa AF: 0.830 Hom.: 27061

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
PhyloP100		0.81
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: rs3988457; hg19: chr8-13348853;