dbSNP rs1060041: DCAF6:p.Asp441Asp (chr1-168004738-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001198956.2(DCAF6):c.1323C>T(p.Asp441Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,613,710 control chromosomes in the GnomAD database, including 48,898 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 0.20 ( 3842 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45056 hom. )

Consequence

DCAF6
NM_001198956.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.217

Publications

19 publications found

Variant links:

Genes affected

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

DCAF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.217 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF6	NM_001198956.2 link	c.1323C>T	p.Asp441Asp	synonymous_variant	Exon 10 of 22	ENST00000367840.4	NP_001185885.1	Q58WW2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF6	ENST00000367840.4 link	c.1323C>T	p.Asp441Asp	synonymous_variant	Exon 10 of 22	1	NM_001198956.2	ENSP00000356814.3		Q58WW2-3

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30879

AN:

151998

Hom.:

3839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.246

AC:

61155

AN:

248920

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.0763

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.241

AC:

352071

AN:

1461594

Hom.:

45056

Cov.:

AF XY:

0.239

AC XY:

174121

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.0739

AC:

2474

AN:

33474

American (AMR)

AF:

0.470

AC:

21016

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6402

AN:

26118

East Asian (EAS)

AF:

0.137

AC:

5444

AN:

39692

South Asian (SAS)

AF:

0.192

AC:

16590

AN:

86244

European-Finnish (FIN)

AF:

0.204

AC:

10873

AN:

53408

Middle Eastern (MID)

AF:

0.250

AC:

1440

AN:

5768

European-Non Finnish (NFE)

AF:

0.247

AC:

274300

AN:

1111792

Other (OTH)

AF:

0.224

AC:

13532

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15097

30194

45290

60387

75484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9362

18724

28086

37448

46810

<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:

0.203

AC:

30891

AN:

152116

Hom.:

3842

Cov.:

AF XY:

0.205

AC XY:

15214

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0809

AC:

3360

AN:

41524

American (AMR)

AF:

0.364

AC:

5550

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

811

AN:

3466

East Asian (EAS)

AF:

0.137

AC:

709

AN:

5176

South Asian (SAS)

AF:

0.189

AC:

914

AN:

4824

European-Finnish (FIN)

AF:

0.209

AC:

2211

AN:

10580

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16475

AN:

67970

Other (OTH)

AF:

0.219

AC:

463

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1190

2380

3570

4760

5950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.225

Hom.:

2674

Bravo

AF:

0.213

Asia WGS

AF:

0.160

AC:

557

AN:

3478

EpiCase

AF:

0.243

EpiControl

AF:

0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.7

(source)

DANN

Benign

0.44

PhyloP100

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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