8-13466930-T-C

Variant names:

• chr8-13466930-T-C
• rs7814428
• NM_182643.3:c.1023+32119A>G

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+32119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 150,444 control chromosomes in the GnomAD database, including 51,379 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 0.82 (51379 hom., cov: 30)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.13
• 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

LOC124901890 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1023+32119A>G		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+32119A>G		intron_variant	Intron 2 of 17	1	NM_182643.3	ENSP00000276297.4
DLC1	ENST00000511869.1	c.1023+32119A>G		intron_variant	Intron 2 of 4	1		ENSP00000425878.1
DLC1	ENST00000316609.9	c.1023+32119A>G		intron_variant	Intron 2 of 5	2		ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.818 AC: 123018 AN: 150334 Hom.: 51371 Cov.: 30

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.818 AC: 123071 AN: 150444 Hom.: 51379 Cov.: 30 AF XY: 0.817 AC XY: 60034 AN XY: 73468

African (AFR) AF: 0.613 AC: 24820 AN: 40468

American (AMR) AF: 0.831 AC: 12567 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3267 AN: 3468

East Asian (EAS) AF: 0.823 AC: 4212 AN: 5118

South Asian (SAS) AF: 0.817 AC: 3869 AN: 4738

European-Finnish (FIN) AF: 0.883 AC: 9161 AN: 10370

Middle Eastern (MID) AF: 0.942 AC: 275 AN: 292

European-Non Finnish (NFE) AF: 0.917 AC: 62238 AN: 67856

Other (OTH) AF: 0.846 AC: 1778 AN: 2102

Alfa AF: 0.881 Hom.: 161003

Bravo AF: 0.798

Asia WGS AF: 0.800 AC: 2784 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	0.32
DANN	Benign	0.29
PhyloP100		-4.1
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: rs7814428; hg19: chr8-13324439;