dbSNP rs609020: DLC1:c.3741-10T>C (chr8-13091442-A-G) – ACMG Classification: Benign (-20 pts)

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.3741-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,609,414 control chromosomes in the GnomAD database, including 254,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27235 hom., cov: 31)

Exomes 𝑓: 0.55 ( 227600 hom. )

Consequence

DLC1
NM_182643.3 intron

Scores

Splicing: ADA: 0.0001604

Clinical Significance

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

Conservation

PhyloP100: 1.44

Publications

14 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 (BayesDel_noAF=-0.7).

BP6

Variant 8-13091442-A-G is Benign according to our data. Variant chr8-13091442-A-G is described in ClinVar as Benign. ClinVar VariationId is 1600292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DLC1	NM_182643.3	MANE Select	c.3741-10T>C	intron	N/A	NP_872584.2	Q96QB1-2
DLC1	NM_001348081.2		c.3741-10T>C	intron	N/A	NP_001335010.1	Q96QB1-2
DLC1	NM_001413124.1		c.3741-10T>C	intron	N/A	NP_001400053.1	Q96QB1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DLC1	ENST00000276297.9	TSL:1 MANE Select	c.3741-10T>C	intron	N/A	ENSP00000276297.4	Q96QB1-2
DLC1	ENST00000358919.6	TSL:1	c.2430-10T>C	intron	N/A	ENSP00000351797.2	Q96QB1-1
DLC1	ENST00000941272.1		c.3741-10T>C	intron	N/A	ENSP00000611331.1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89744

AN:

151804

Hom.:

27204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.548

GnomAD2 exomes

AF:

0.545

AC:

136500

AN:

250642

AF XY:

0.555

show subpopulations

Gnomad AFR exome

AF:

0.724

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.624

Gnomad EAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.557

GnomAD4 exome

AF:

0.555

AC:

808818

AN:

1457492

Hom.:

227600

Cov.:

AF XY:

0.559

AC XY:

405124

AN XY:

725242

show subpopulations

African (AFR)

AF:

0.726

AC:

24225

AN:

33346

American (AMR)

AF:

0.371

AC:

16525

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

16153

AN:

26064

East Asian (EAS)

AF:

0.369

AC:

14632

AN:

39666

South Asian (SAS)

AF:

0.657

AC:

56442

AN:

85948

European-Finnish (FIN)

AF:

0.542

AC:

28927

AN:

53352

Middle Eastern (MID)

AF:

0.649

AC:

3728

AN:

5746

European-Non Finnish (NFE)

AF:

0.554

AC:

614090

AN:

1108616

Other (OTH)

AF:

0.566

AC:

34096

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17928

35856

53783

71711

89639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17236

34472

51708

68944

86180

<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:

0.591

AC:

89824

AN:

151922

Hom.:

27235

Cov.:

AF XY:

0.592

AC XY:

43969

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.718

AC:

29725

AN:

41422

American (AMR)

AF:

0.478

AC:

7297

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

2155

AN:

3468

East Asian (EAS)

AF:

0.384

AC:

1977

AN:

5144

South Asian (SAS)

AF:

0.663

AC:

3185

AN:

4806

European-Finnish (FIN)

AF:

0.545

AC:

5754

AN:

10558

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

38020

AN:

67942

Other (OTH)

AF:

0.547

AC:

1155

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1826

3652

5477

7303

9129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.566

Hom.:

15355

Bravo

AF:

0.584

Asia WGS

AF:

0.510

AC:

1777

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.5

(source)

DANN

Benign

0.83

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.034

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over