rs12541254

Variant names:

• chr8-13121891-G-A
• rs12541254
• NM_182643.3:c.1349-6234C>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.1349-6234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,830 control chromosomes in the GnomAD database, including 10,703 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 0.36 (10703 hom., cov: 31)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1349-6234C>T		intron_variant	Intron 5 of 17	ENST00000276297.9	NP_872584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9	c.1349-6234C>T		intron_variant	Intron 5 of 17	1	NM_182643.3	ENSP00000276297.4

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55193 AN: 151712 Hom.: 10683 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.364 AC: 55258 AN: 151830 Hom.: 10703 Cov.: 31 AF XY: 0.360 AC XY: 26695 AN XY: 74204

African (AFR) AF: 0.473 AC: 19579 AN: 41366

American (AMR) AF: 0.243 AC: 3706 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3466

East Asian (EAS) AF: 0.127 AC: 654 AN: 5158

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4800

European-Finnish (FIN) AF: 0.358 AC: 3773 AN: 10534

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23792 AN: 67940

Other (OTH) AF: 0.344 AC: 724 AN: 2104

Alfa AF: 0.347 Hom.: 30541

Bravo AF: 0.352

Asia WGS AF: 0.272 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.79
PhyloP100		-0.30
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: rs12541254; hg19: chr8-12979400;