chr8-13331883-A-T

Variant names:

• chr8-13331883-A-T
• rs1454947
• NM_182643.3:c.1315-26581T>A

Variant summary

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

The NM_182643.3(DLC1):​c.1315-26581T>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
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182643.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	NM_182643.3	MANE Select	c.1315-26581T>A		intron	N/A	NP_872584.2	Q96QB1-2
	DLC1	NM_001348081.2		c.1315-26581T>A		intron	N/A	NP_001335010.1	Q96QB1-2
	DLC1	NM_001413124.1		c.1315-26581T>A		intron	N/A	NP_001400053.1	Q96QB1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	ENST00000276297.9	TSL:1 MANE Select	c.1315-26581T>A		intron	N/A	ENSP00000276297.4	Q96QB1-2
	DLC1	ENST00000511869.1	TSL:1	c.1315-26581T>A		intron	N/A	ENSP00000425878.1	Q96QB1-5
	DLC1	ENST00000941272.1		c.1315-26581T>A		intron	N/A	ENSP00000611331.1

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

African (AFR) AF: 0.748 AC: 31013 AN: 41468

American (AMR) AF: 0.920 AC: 14077 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3224 AN: 3472

East Asian (EAS) AF: 0.951 AC: 4910 AN: 5162

South Asian (SAS) AF: 0.863 AC: 4165 AN: 4824

European-Finnish (FIN) AF: 0.881 AC: 9332 AN: 10592

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60542 AN: 68034

Other (OTH) AF: 0.876 AC: 1850 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.48
PhyloP100		0.56
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: rs1454947; hg19: chr8-13189392;