Genetic Variant DCAF12:c.540+125A>G (chr9-34107234-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 ENST00000361264.9(DCAF12):c.540+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 908,578 control chromosomes in the GnomAD database, including 242,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.70 ( 38052 hom., cov: 31)

Exomes 𝑓: 0.73 ( 204185 hom. )

Consequence

DCAF12
ENST00000361264.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.333

Publications

12 publications found

Variant links:

Genes affected

DCAF12 (HGNC:19911): (DDB1 and CUL4 associated factor 12) This gene encodes a WD repeat-containing protein that interacts with the COP9 signalosome, a macromolecular complex that interacts with cullin-RING E3 ligases and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. [provided by RefSeq, Jul 2009]

DCAF12 links:

ENSG00000228352 (HGNC:58097):

ENSG00000228352 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361264.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF12	NM_015397.4	MANE Select	c.540+125A>G		intron	N/A	NP_056212.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DCAF12	ENST00000361264.9	TSL:1 MANE Select	c.540+125A>G	intron	N/A	ENSP00000355114.3
DCAF12	ENST00000396990.6	TSL:3	c.486+125A>G	intron	N/A	ENSP00000380187.2
DCAF12	ENST00000450964.1	TSL:5	c.477+125A>G	intron	N/A	ENSP00000415833.1

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106434

AN:

151872

Hom.:

38020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.713

GnomAD4 exome

AF:

0.726

AC:

549458

AN:

756588

Hom.:

204185

AF XY:

0.726

AC XY:

286444

AN XY:

394742

show subpopulations

African (AFR)

AF:

0.628

AC:

12487

AN:

19882

American (AMR)

AF:

0.651

AC:

22641

AN:

34756

Ashkenazi Jewish (ASJ)

AF:

0.755

AC:

14248

AN:

18860

East Asian (EAS)

AF:

0.285

AC:

10067

AN:

35334

South Asian (SAS)

AF:

0.680

AC:

43129

AN:

63412

European-Finnish (FIN)

AF:

0.756

AC:

35251

AN:

46654

Middle Eastern (MID)

AF:

0.704

AC:

1882

AN:

2674

European-Non Finnish (NFE)

AF:

0.769

AC:

383275

AN:

498210

Other (OTH)

AF:

0.719

AC:

26478

AN:

36806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

7389

14777

22166

29554

36943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5524

11048

16572

22096

27620

<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:

0.701

AC:

106514

AN:

151990

Hom.:

38052

Cov.:

AF XY:

0.697

AC XY:

51748

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.633

AC:

26241

AN:

41456

American (AMR)

AF:

0.669

AC:

10199

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

2623

AN:

3470

East Asian (EAS)

AF:

0.328

AC:

1695

AN:

5164

South Asian (SAS)

AF:

0.682

AC:

3283

AN:

4812

European-Finnish (FIN)

AF:

0.746

AC:

7877

AN:

10562

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.769

AC:

52231

AN:

67964

Other (OTH)

AF:

0.714

AC:

1507

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1578

3157

4735

6314

7892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.731

Hom.:

17458

Bravo

AF:

0.686

Asia WGS

AF:

0.540

AC:

1875

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

(source)

DANN

Benign

0.61

PhyloP100

-0.33

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over