rs3816747

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.779C>T(p.Thr260Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,614,014 control chromosomes in the GnomAD database, including 680,659 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 0.89 ( 60501 hom., cov: 33)

Exomes 𝑓: 0.92 ( 620158 hom. )

Consequence

DLC1
NM_182643.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.09

Publications

38 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=7.642247E-7).

BP6

Variant 8-13499293-G-A is Benign according to our data. Variant chr8-13499293-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3 link	c.779C>T	p.Thr260Ile	missense_variant	Exon 2 of 18	ENST00000276297.9	NP_872584.2	Q96QB1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLC1	ENST00000276297.9 link	c.779C>T	p.Thr260Ile	missense_variant	Exon 2 of 18	1	NM_182643.3	ENSP00000276297.4	Q96QB1-2
DLC1	ENST00000511869.1 link	c.779C>T	p.Thr260Ile	missense_variant	Exon 2 of 5	1		ENSP00000425878.1	Q96QB1-5
DLC1	ENST00000316609.9 link	c.779C>T	p.Thr260Ile	missense_variant	Exon 2 of 6	2		ENSP00000321034.5	Q96QB1-3
DLC1	ENST00000517868.2 link	c.-53C>T		upstream_gene_variant		6		ENSP00000473289.1	R4GMP5

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

135081

AN:

152128

Hom.:

60458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.974

Gnomad AMR

AF:

0.781

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.938

Gnomad OTH

AF:

0.883

GnomAD2 exomes

AF:

0.869

AC:

218119

AN:

251102

AF XY:

0.880

show subpopulations

Gnomad AFR exome

AF:

0.862

Gnomad AMR exome

AF:

0.686

Gnomad ASJ exome

AF:

0.916

Gnomad EAS exome

AF:

0.602

Gnomad FIN exome

AF:

0.931

Gnomad NFE exome

AF:

0.939

Gnomad OTH exome

AF:

0.883

GnomAD4 exome

AF:

0.918

AC:

1342592

AN:

1461768

Hom.:

620158

Cov.:

AF XY:

0.920

AC XY:

668779

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.864

AC:

28915

AN:

33456

American (AMR)

AF:

0.693

AC:

30979

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

23940

AN:

26134

East Asian (EAS)

AF:

0.623

AC:

24728

AN:

39698

South Asian (SAS)

AF:

0.916

AC:

78986

AN:

86258

European-Finnish (FIN)

AF:

0.933

AC:

49810

AN:

53404

Middle Eastern (MID)

AF:

0.931

AC:

5366

AN:

5766

European-Non Finnish (NFE)

AF:

0.940

AC:

1045256

AN:

1111966

Other (OTH)

AF:

0.904

AC:

54612

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

6701

13402

20103

26804

33505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21512

43024

64536

86048

107560

<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:

0.888

AC:

135182

AN:

152246

Hom.:

60501

Cov.:

AF XY:

0.884

AC XY:

65787

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.862

AC:

35793

AN:

41524

American (AMR)

AF:

0.781

AC:

11933

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.913

AC:

3170

AN:

3472

East Asian (EAS)

AF:

0.619

AC:

3203

AN:

5178

South Asian (SAS)

AF:

0.910

AC:

4395

AN:

4828

European-Finnish (FIN)

AF:

0.929

AC:

9846

AN:

10602

Middle Eastern (MID)

AF:

0.925

AC:

272

AN:

294

European-Non Finnish (NFE)

AF:

0.938

AC:

63811

AN:

68036

Other (OTH)

AF:

0.885

AC:

1871

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

747

1493

2240

2986

3733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.912

Hom.:

219596

Bravo

AF:

0.871

TwinsUK

AF:

0.947

AC:

3511

ALSPAC

AF:

0.936

AC:

3606

ESP6500AA

AF:

0.865

AC:

3813

ESP6500EA

AF:

0.933

AC:

8024

ExAC

AF:

0.878

AC:

106560

Asia WGS

AF:

0.810

AC:

2819

AN:

3478

EpiCase

AF:

0.937

EpiControl

AF:

0.933

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26095787) -

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

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.011

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.039

T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.14

T;.;.

MetaRNN

Benign

7.6e-7

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.2

N;N;N

PhyloP100

-1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.50

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.067

MPC

0.024

ClinPred

0.039

GERP RS

-10

PromoterAI

0.0026

Neutral

(source)

Varity_R

0.035

gMVP

0.037

Mutation Taster

=96/4

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