rs3816748

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182643.3(DLC1):c.241C>G(p.Leu81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,030 control chromosomes in the GnomAD database, including 2,550 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 311 hom., cov: 33)

Exomes 𝑓: 0.026 ( 2239 hom. )

Consequence

DLC1
NM_182643.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.15

Publications

16 publications found

Variant links:

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

DLC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001494199).

BP6

Variant 8-13499831-G-C is Benign according to our data. Variant chr8-13499831-G-C is described in ClinVar as Benign. ClinVar VariationId is 1600976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3 link	c.241C>G	p.Leu81Val	missense_variant	Exon 2 of 18	ENST00000276297.9	NP_872584.2	Q96QB1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLC1	ENST00000276297.9 link	c.241C>G	p.Leu81Val	missense_variant	Exon 2 of 18	1	NM_182643.3	ENSP00000276297.4		Q96QB1-2

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5123

AN:

152144

Hom.:

310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.0979

Gnomad FIN

AF:

0.0320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.0345

GnomAD2 exomes

AF:

0.0617

AC:

15517

AN:

251324

AF XY:

0.0569

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.00883

Gnomad OTH exome

AF:

0.0398

GnomAD4 exome

AF:

0.0258

AC:

37663

AN:

1461768

Hom.:

2239

Cov.:

AF XY:

0.0266

AC XY:

19337

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0188

AC:

630

AN:

33480

American (AMR)

AF:

0.171

AC:

7630

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00677

AC:

177

AN:

26134

East Asian (EAS)

AF:

0.209

AC:

8310

AN:

39698

South Asian (SAS)

AF:

0.0871

AC:

7516

AN:

86258

European-Finnish (FIN)

AF:

0.0278

AC:

1482

AN:

53336

Middle Eastern (MID)

AF:

0.00745

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00896

AC:

9965

AN:

1111978

Other (OTH)

AF:

0.0316

AC:

1910

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

2329

4658

6988

9317

11646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0337

AC:

5126

AN:

152262

Hom.:

311

Cov.:

AF XY:

0.0373

AC XY:

2780

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0211

AC:

879

AN:

41566

American (AMR)

AF:

0.104

AC:

1594

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.225

AC:

1163

AN:

5176

South Asian (SAS)

AF:

0.0976

AC:

471

AN:

4826

European-Finnish (FIN)

AF:

0.0320

AC:

339

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00853

AC:

580

AN:

68016

Other (OTH)

AF:

0.0360

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

222

443

665

886

1108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0173

Hom.:

106

Bravo

AF:

0.0398

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.0195

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.0560

AC:

6804

Asia WGS

AF:

0.138

AC:

477

AN:

3476

EpiCase

AF:

0.00703

EpiControl

AF:

0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.053

(source)

DANN

Benign

0.097

DEOGEN2

Benign

0.029

T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.52

T;.;.;.

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.90

N;N;N;.

PhyloP100

-1.1

PrimateAI

Benign

0.25

PROVEAN

Benign

0.17

N;N;N;.

REVEL

Benign

0.018

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

0.75

T;T;T;.

Polyphen

0.0

B;B;.;.

Vest4

0.043

MPC

0.023

ClinPred

0.0093

GERP RS

-5.5

Varity_R

0.032

gMVP

0.024

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over