NM_182643.3:c.1821G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182643.3(DLC1):c.1821G>T(p.Ala607Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,611,792 control chromosomes in the GnomAD database, including 99,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7898 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92002 hom. )

Consequence

DLC1
NM_182643.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.02

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 8-13100516-C-A is Benign according to our data. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-13100516-C-A is described in CliVar as Benign. Clinvar id is 1280889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLC1	NM_182643.3 link	c.1821G>T	p.Ala607Ala	synonymous_variant	Exon 9 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.1821G>T	p.Ala607Ala	synonymous_variant	Exon 9 of 18	1	NM_182643.3	ENSP00000276297.4		Q96QB1-2

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45778

AN:

151660

Hom.:

7885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.587

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.347

GnomAD2 exomes

AF:

0.372

AC:

92134

AN:

248004

AF XY:

0.361

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.586

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.347

AC:

506127

AN:

1460014

Hom.:

92002

Cov.:

AF XY:

0.344

AC XY:

250066

AN XY:

726394

show subpopulations

African (AFR)

AF:

0.145

AC:

4851

AN:

33478

American (AMR)

AF:

0.574

AC:

25655

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7143

AN:

26134

East Asian (EAS)

AF:

0.593

AC:

23549

AN:

39700

South Asian (SAS)

AF:

0.295

AC:

25408

AN:

86254

European-Finnish (FIN)

AF:

0.355

AC:

18347

AN:

51704

Middle Eastern (MID)

AF:

0.224

AC:

1287

AN:

5756

European-Non Finnish (NFE)

AF:

0.341

AC:

379307

AN:

1111902

Other (OTH)

AF:

0.341

AC:

20580

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

23232

46464

69695

92927

116159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12338

24676

37014

49352

61690

<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:

0.302

AC:

45799

AN:

151778

Hom.:

7898

Cov.:

AF XY:

0.301

AC XY:

22345

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.155

AC:

6417

AN:

41414

American (AMR)

AF:

0.439

AC:

6699

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

910

AN:

3470

East Asian (EAS)

AF:

0.587

AC:

3003

AN:

5116

South Asian (SAS)

AF:

0.297

AC:

1428

AN:

4804

European-Finnish (FIN)

AF:

0.353

AC:

3716

AN:

10526

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22557

AN:

67884

Other (OTH)

AF:

0.350

AC:

738

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1475

2950

4424

5899

7374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.315

Hom.:

2419

Bravo

AF:

0.312

Asia WGS

AF:

0.454

AC:

1577

AN:

3478

EpiCase

AF:

0.331

EpiControl

AF:

0.330

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 27, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.6

(source)

DANN

Benign

0.62

PhyloP100

-1.0

Mutation Taster

=100/0

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