NM_182643.3:c.1315-13596T>C

Variant names:

• chr8-13318898-A-G
• rs1671400
• NM_182643.3:c.1315-13596T>C

Variant summary

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

The NM_182643.3(DLC1):​c.1315-13596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,198 control chromosomes in the GnomAD database, including 56,917 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 (56917 hom., cov: 33)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3	c.1315-13596T>C		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.1315-13596T>C		intron_variant	Intron 4 of 17	1	NM_182643.3	ENSP00000276297.4
DLC1	ENST00000511869.1	c.1315-13596T>C		intron_variant	Intron 4 of 4	1		ENSP00000425878.1
DLC1	ENST00000316609.9	c.1315-13596T>C		intron_variant	Intron 4 of 5	2		ENSP00000321034.5

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131372 AN: 152080 Hom.: 56891 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.864 AC: 131447 AN: 152198 Hom.: 56917 Cov.: 33 AF XY: 0.864 AC XY: 64322 AN XY: 74424

African (AFR) AF: 0.832 AC: 34546 AN: 41498

American (AMR) AF: 0.852 AC: 13033 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2915 AN: 3472

East Asian (EAS) AF: 0.963 AC: 4977 AN: 5166

South Asian (SAS) AF: 0.776 AC: 3740 AN: 4820

European-Finnish (FIN) AF: 0.938 AC: 9948 AN: 10602

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59561 AN: 68022

Other (OTH) AF: 0.845 AC: 1788 AN: 2116

Alfa AF: 0.869 Hom.: 177514

Bravo AF: 0.860

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.70
PhyloP100		0.70
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: rs1671400; hg19: chr8-13176407;