rs145189179

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_001198956.2(DCAF6):c.2240G>A(p.Arg747Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000498 in 1,607,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

DCAF6
NM_001198956.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1

Conservation

PhyloP100: 5.20

Publications

4 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: Likely_benign. The variant received -1 ACMG points.

PP5

Variant 1-168045209-G-A is Pathogenic according to our data. Variant chr1-168045209-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 224814.

BP4

Computational evidence support a benign effect (MetaRNN=0.14479268). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAd4 at 57 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF6	NM_001198956.2 link	c.2240G>A	p.Arg747Gln	missense_variant	Exon 16 of 22	ENST00000367840.4	NP_001185885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF6	ENST00000367840.4 link	c.2240G>A	p.Arg747Gln	missense_variant	Exon 16 of 22	1	NM_001198956.2	ENSP00000356814.3

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000720

AC:

176

AN:

244578

AF XY:

0.000763

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.000209

Gnomad EAS exome

AF:

0.0000549

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000959

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000510

AC:

743

AN:

1455566

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

400

AN XY:

723534

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33092

American (AMR)

AF:

0.00106

AC:

AN:

43582

Ashkenazi Jewish (ASJ)

AF:

0.000194

AC:

AN:

25718

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39624

South Asian (SAS)

AF:

0.000764

AC:

AN:

85088

European-Finnish (FIN)

AF:

0.000375

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.00315

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.000482

AC:

535

AN:

1109366

Other (OTH)

AF:

0.000832

AC:

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000375

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41438

American (AMR)

AF:

0.00118

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.000733

Hom.:

Bravo

AF:

0.000525

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Cerebral visual impairment and intellectual disability

Pathogenic:1

Sep 09, 2015

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

This study shows that diverse genetic causes underlie CVI. -

DCAF6-related condition

Uncertain:1

Jul 04, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;.;T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.5

.;.;L;.

PhyloP100

5.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.012

D;T;D;D

Sift4G

Uncertain

0.034

D;T;T;D

Polyphen

1.0

.;D;D;D

Vest4

0.60

MVP

0.58

MPC

1.2

ClinPred

0.36

GERP RS

4.5

Varity_R

0.14

gMVP

0.52

Mutation Taster

=90/10

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over