Variant 14-24117358-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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:

DCAF11 (HGNC:):

DCAF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
DCAF11	NM_025230.5 linkuse as main transcript	c.376G>A	p.Ala126Thr	missense_variant	4/15	ENST00000446197.8	NP_079506.3	Q8TEB1-1Q59GN6B3KSW2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF11	ENST00000446197.8 linkuse as main transcript	c.376G>A	p.Ala126Thr	missense_variant	4/15	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

GnomAD3 exomes

AF:

0.00563

AC:

1414

AN:

251362

Hom.:

AF XY:

0.00397

AC XY:

539

AN XY:

135898

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 SAS exome

AF:

0.000229

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

Gnomad4 AFR exome

AF:

0.0866

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00523

GnomAD4 genome

AF:

0.0228

AC:

3472

AN:

152264

Hom.:

120

Cov.:

AF XY:

0.0218

AC XY:

1623

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0800

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.00395

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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;.;.;.;.;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over