rs536147

Variant names:

• chr8-13114798-C-G
• rs536147
• NM_182643.3:c.1420+788G>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.1420+788G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,170 control chromosomes in the GnomAD database, including 50,377 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 0.81 (50377 hom., cov: 32)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	NM_182643.3	MANE Select	c.1420+788G>C		intron	N/A	NP_872584.2
	DLC1	NM_001348081.2		c.1420+788G>C		intron	N/A	NP_001335010.1
	DLC1	NM_001413124.1		c.1420+788G>C		intron	N/A	NP_001400053.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLC1	ENST00000276297.9	TSL:1 MANE Select	c.1420+788G>C		intron	N/A	ENSP00000276297.4
	DLC1	ENST00000358919.6	TSL:1	c.109+788G>C		intron	N/A	ENSP00000351797.2
	DLC1	ENST00000512044.6	TSL:2	c.211+788G>C		intron	N/A	ENSP00000422595.2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123505 AN: 152052 Hom.: 50331 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.812 AC: 123610 AN: 152170 Hom.: 50377 Cov.: 32 AF XY: 0.814 AC XY: 60547 AN XY: 74396

African (AFR) AF: 0.796 AC: 33030 AN: 41486

American (AMR) AF: 0.856 AC: 13091 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2686 AN: 3468

East Asian (EAS) AF: 0.958 AC: 4956 AN: 5172

South Asian (SAS) AF: 0.912 AC: 4396 AN: 4822

European-Finnish (FIN) AF: 0.794 AC: 8412 AN: 10600

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54491 AN: 68014

Other (OTH) AF: 0.820 AC: 1730 AN: 2110

Alfa AF: 0.805 Hom.: 6136

Bravo AF: 0.818

Asia WGS AF: 0.921 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.59
PhyloP100		-1.6
Mutation Taster		=99/1	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: rs536147; hg19: chr8-12972307;