Genetic Variant DEPDC1:c.769+50_769+55dupGTGTGT (chr1-68486881-A-AACACAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001114120.3(DEPDC1):c.769+50_769+55dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,177,150 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 0)

Exomes 𝑓: 0.00053 ( 0 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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+50_769+55dupGTGTGT		intron	N/A	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.769+50_769+55dupGTGTGT		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+56insGTGTGT	intron	N/A	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9	TSL:1	c.769+55_769+56insGTGTGT	intron	N/A	ENSP00000360005.5	Q5TB30-2
DEPDC1	ENST00000489862.1	TSL:1	n.472+55_472+56insGTGTGT	intron	N/A	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

225

AN:

143634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000494

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.00160

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000459

Gnomad OTH

AF:

0.00102

GnomAD4 exome

AF:

0.000525

AC:

543

AN:

1033424

Hom.:

AF XY:

0.000544

AC XY:

275

AN XY:

505356

show subpopulations

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

African (AFR)

AF:

0.000753

AC:

AN:

22586

American (AMR)

AF:

0.000502

AC:

AN:

17930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15440

East Asian (EAS)

AF:

0.000793

AC:

AN:

30256

South Asian (SAS)

AF:

0.000994

AC:

AN:

30192

European-Finnish (FIN)

AF:

0.00607

AC:

251

AN:

41370

Middle Eastern (MID)

AF:

0.000302

AC:

AN:

3316

European-Non Finnish (NFE)

AF:

0.000222

AC:

184

AN:

830006

Other (OTH)

AF:

0.000638

AC:

AN:

42328

⚠️ 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: 0.314

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00157

AC:

226

AN:

143726

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

146

AN XY:

69602

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

38946

American (AMR)

AF:

0.000493

AC:

AN:

14192

Ashkenazi Jewish (ASJ)

AF:

0.000299

AC:

AN:

3350

East Asian (EAS)

AF:

0.00310

AC:

AN:

4842

South Asian (SAS)

AF:

0.00183

AC:

AN:

4380

European-Finnish (FIN)

AF:

0.0108

AC:

102

AN:

9438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000459

AC:

AN:

65420

Other (OTH)

AF:

0.00101

AC:

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000882

Hom.:

278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-68486881-AACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACAC

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