Genetic Variant DEPDC1:c.769+54_769+55dupGT (chr1-68486881-A-AAC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001114120.3(DEPDC1):c.769+54_769+55dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,166,452 control chromosomes in the GnomAD database, including 573 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.090 ( 529 hom., cov: 0)

Exomes 𝑓: 0.062 ( 44 hom. )

Consequence

DEPDC1
NM_001114120.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 publications found

Variant links:

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114120.3. 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
	DEPDC1	NM_001114120.3	MANE Select	c.769+54_769+55dupGT		intron	N/A	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.769+54_769+55dupGT		intron	N/A	NP_060249.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DEPDC1	ENST00000456315.7	TSL:1 MANE Select	c.769+55_769+56insGT	intron	N/A	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9	TSL:1	c.769+55_769+56insGT	intron	N/A	ENSP00000360005.5	Q5TB30-2
DEPDC1	ENST00000489862.1	TSL:1	n.472+55_472+56insGT	intron	N/A	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes

AF:

0.0903

AC:

12951

AN:

143494

Hom.:

529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0681

Gnomad AMI

AF:

0.0919

Gnomad AMR

AF:

0.0916

Gnomad ASJ

AF:

0.0517

Gnomad EAS

AF:

0.0953

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0619

AC:

63337

AN:

1022866

Hom.:

AF XY:

0.0625

AC XY:

31257

AN XY:

500314

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0454

AC:

1016

AN:

22398

American (AMR)

AF:

0.0548

AC:

976

AN:

17816

Ashkenazi Jewish (ASJ)

AF:

0.0433

AC:

665

AN:

15348

East Asian (EAS)

AF:

0.0663

AC:

1994

AN:

30074

South Asian (SAS)

AF:

0.0362

AC:

1089

AN:

30070

European-Finnish (FIN)

AF:

0.114

AC:

4690

AN:

41040

Middle Eastern (MID)

AF:

0.0829

AC:

272

AN:

3282

European-Non Finnish (NFE)

AF:

0.0609

AC:

50005

AN:

820932

Other (OTH)

AF:

0.0628

AC:

2630

AN:

41906

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.359

Heterozygous variant carriers

3404

6808

10212

13616

17020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1866

3732

5598

7464

9330

<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:

0.0903

AC:

12962

AN:

143586

Hom.:

529

Cov.:

AF XY:

0.0913

AC XY:

6350

AN XY:

69526

show subpopulations

African (AFR)

AF:

0.0680

AC:

2644

AN:

38906

American (AMR)

AF:

0.0921

AC:

1305

AN:

14174

Ashkenazi Jewish (ASJ)

AF:

0.0517

AC:

173

AN:

3348

East Asian (EAS)

AF:

0.0957

AC:

463

AN:

4838

South Asian (SAS)

AF:

0.0524

AC:

229

AN:

4374

European-Finnish (FIN)

AF:

0.133

AC:

1253

AN:

9422

Middle Eastern (MID)

AF:

0.108

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.101

AC:

6581

AN:

65372

Other (OTH)

AF:

0.102

AC:

201

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

533

1066

1600

2133

2666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.103

Hom.:

278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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