8-13086182-C-T

Variant names:

• chr8-13086182-C-T
• rs621554
• NM_182643.3:c.4466+108G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182643.3(DLC1):​c.4466+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,439,722 control chromosomes in the GnomAD database, including 189,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20587 hom., cov: 33)
  • Exomes 𝑓: 0.51 (168674 hom.)
• Consequence: DLC1 NM_182643.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.800
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-13086182-C-T is Benign according to our data. Variant chr8-13086182-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.619 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.4466+108G>A		intron	N/A	NP_872584.2	Q96QB1-2
	DLC1	NM_001348081.2		c.4466+108G>A		intron	N/A	NP_001335010.1	Q96QB1-2
	DLC1	NM_001413124.1		c.4466+108G>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.4466+108G>A		intron	N/A	ENSP00000276297.4	Q96QB1-2
	DLC1	ENST00000358919.6	TSL:1	c.3155+108G>A		intron	N/A	ENSP00000351797.2	Q96QB1-1
	DLC1	ENST00000941272.1		c.4466+108G>A		intron	N/A	ENSP00000611331.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78664 AN: 151932 Hom.: 20564 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.509 AC: 655134 AN: 1287672 Hom.: 168674 Cov.: 20 AF XY: 0.512 AC XY: 324579 AN XY: 633468

African (AFR) AF: 0.573 AC: 16340 AN: 28500

American (AMR) AF: 0.364 AC: 10399 AN: 28606

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 10891 AN: 19766

East Asian (EAS) AF: 0.343 AC: 12985 AN: 37828

South Asian (SAS) AF: 0.630 AC: 41857 AN: 66464

European-Finnish (FIN) AF: 0.473 AC: 21069 AN: 44502

Middle Eastern (MID) AF: 0.595 AC: 2407 AN: 4044

European-Non Finnish (NFE) AF: 0.509 AC: 511626 AN: 1004316

Other (OTH) AF: 0.514 AC: 27560 AN: 53646

GnomAD4 genome AF: 0.518 AC: 78729 AN: 152050 Hom.: 20587 Cov.: 33 AF XY: 0.518 AC XY: 38517 AN XY: 74320

African (AFR) AF: 0.569 AC: 23611 AN: 41472

American (AMR) AF: 0.438 AC: 6696 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1884 AN: 5174

South Asian (SAS) AF: 0.638 AC: 3075 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5038 AN: 10556

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34948 AN: 67960

Other (OTH) AF: 0.496 AC: 1049 AN: 2114

Alfa AF: 0.504 Hom.: 7492

Bravo AF: 0.510

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-0.80
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: rs621554; hg19: chr8-12943691; COSMIC: COSV107305585; COSMIC: COSV107305585;