Genetic Variant DCUN1D1:c.221-16A>G (chr3-182964065-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020640.4(DCUN1D1):c.221-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,596,022 control chromosomes in the GnomAD database, including 317,861 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 22229 hom., cov: 32)

Exomes 𝑓: 0.63 ( 295632 hom. )

Consequence

DCUN1D1
NM_020640.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

Publications

17 publications found

Variant links:

Genes affected

DCUN1D1 (HGNC:18184): (defective in cullin neddylation 1 domain containing 1) Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation and regulation of protein ubiquitination. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

DCUN1D1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCUN1D1	NM_020640.4 link	c.221-16A>G		intron_variant	Intron 2 of 6	ENST00000292782.9	NP_065691.2	Q96GG9B4DM76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCUN1D1	ENST00000292782.9 link	c.221-16A>G		intron_variant	Intron 2 of 6	1	NM_020640.4	ENSP00000292782.4		Q96GG9

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73645

AN:

151966

Hom.:

22244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.559

AC:

138052

AN:

247146

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.655

Gnomad OTH exome

AF:

0.577

GnomAD4 exome

AF:

0.627

AC:

905798

AN:

1443940

Hom.:

295632

Cov.:

AF XY:

0.627

AC XY:

450128

AN XY:

718272

show subpopulations

African (AFR)

AF:

0.104

AC:

3454

AN:

33142

American (AMR)

AF:

0.565

AC:

24567

AN:

43514

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

12772

AN:

25748

East Asian (EAS)

AF:

0.190

AC:

7500

AN:

39488

South Asian (SAS)

AF:

0.556

AC:

47136

AN:

84796

European-Finnish (FIN)

AF:

0.673

AC:

35535

AN:

52814

Middle Eastern (MID)

AF:

0.506

AC:

2895

AN:

5720

European-Non Finnish (NFE)

AF:

0.670

AC:

736910

AN:

1099080

Other (OTH)

AF:

0.587

AC:

35029

AN:

59638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13426

26853

40279

53706

67132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18648

37296

55944

74592

93240

<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:

0.484

AC:

73606

AN:

152082

Hom.:

22229

Cov.:

AF XY:

0.485

AC XY:

36040

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.125

AC:

5190

AN:

41492

American (AMR)

AF:

0.555

AC:

8462

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

1691

AN:

3470

East Asian (EAS)

AF:

0.233

AC:

1207

AN:

5170

South Asian (SAS)

AF:

0.552

AC:

2658

AN:

4816

European-Finnish (FIN)

AF:

0.676

AC:

7154

AN:

10578

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.668

AC:

45413

AN:

67984

Other (OTH)

AF:

0.494

AC:

1044

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1537

3074

4610

6147

7684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.612

Hom.:

10080

Bravo

AF:

0.457

Asia WGS

AF:

0.359

AC:

1251

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.71

(source)

DANN

Benign

0.37

PhyloP100

-0.11

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

Computational scores

Splicing

Publications

Other links and lift over