Genetic Variant DCAF11:p.Ala126Thr (chr14-24117358-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025230.5(DCAF11):c.376G>A(p.Ala126Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,614,148 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 120 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 142 hom. )

Consequence

DCAF11
NM_025230.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.579

Publications

5 publications found

Variant links:

Genes affected

DCAF11 (HGNC:20258): (DDB1 and CUL4 associated factor 11) 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. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

DCAF11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017348826).

BP6

Variant 14-24117358-G-A is Benign according to our data. Variant chr14-24117358-G-A is described in ClinVar as Benign. ClinVar VariationId is 768640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF11	NM_025230.5 link	c.376G>A	p.Ala126Thr	missense_variant	Exon 4 of 15	ENST00000446197.8	NP_079506.3	Q8TEB1-1Q59GN6B3KSW2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF11	ENST00000446197.8 link	c.376G>A	p.Ala126Thr	missense_variant	Exon 4 of 15	1	NM_025230.5	ENSP00000415556.4		Q8TEB1-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3452

AN:

152146

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0798

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.00563

AC:

1414

AN:

251362

AF XY:

0.00397

show subpopulations

Gnomad AFR exome

AF:

0.0788

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00236

AC:

3457

AN:

1461884

Hom.:

142

Cov.:

AF XY:

0.00202

AC XY:

1469

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0866

AC:

2900

AN:

33478

American (AMR)

AF:

0.00338

AC:

151

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.000301

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1112012

Other (OTH)

AF:

0.00523

AC:

316

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

193

386

579

772

965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0228

AC:

3472

AN:

152264

Hom.:

120

Cov.:

AF XY:

0.0218

AC XY:

1623

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0800

AC:

3321

AN:

41516

American (AMR)

AF:

0.00614

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

165

330

494

659

824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00828

Hom.:

Bravo

AF:

0.0262

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0740

AC:

326

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00698

AC:

848

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.011

T;.;T;T;T;.;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.062

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;N;.;.;.;.;.;.

PhyloP100

0.58

PrimateAI

Benign

0.36

PROVEAN

Benign

0.80

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.55

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;T;T;T;T

Polyphen

0.0010

B;.;B;.;.;.;.;.;B

Vest4

0.20

MVP

0.061

MPC

0.34

ClinPred

0.0019

GERP RS

0.62

Varity_R

0.017

gMVP

0.39

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over