dbSNP rs10857636: WDFY4:c.3098+81C>T (chr10-48777065-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394531.1(WDFY4):c.3098+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,420,572 control chromosomes in the GnomAD database, including 2,332 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 0.055 ( 264 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2068 hom. )

Consequence

WDFY4
NM_001394531.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.37

Publications

11 publications found

Variant links:

Genes affected

WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

WDFY4 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

WDFY4 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1 link	c.3098+81C>T		intron_variant	Intron 16 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12 link	c.3098+81C>T		intron_variant	Intron 16 of 61	5	NM_001394531.1	ENSP00000320563.5		Q6ZS81-1

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8401

AN:

152142

Hom.:

261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.0869

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0583

Gnomad OTH

AF:

0.0565

GnomAD4 exome

AF:

0.0552

AC:

70006

AN:

1268312

Hom.:

2068

AF XY:

0.0549

AC XY:

34233

AN XY:

623014

show subpopulations

African (AFR)

AF:

0.0581

AC:

1646

AN:

28316

American (AMR)

AF:

0.0319

AC:

953

AN:

29842

Ashkenazi Jewish (ASJ)

AF:

0.0592

AC:

1237

AN:

20880

East Asian (EAS)

AF:

0.000115

AC:

AN:

34872

South Asian (SAS)

AF:

0.0369

AC:

2474

AN:

66998

European-Finnish (FIN)

AF:

0.0856

AC:

4011

AN:

46856

Middle Eastern (MID)

AF:

0.0688

AC:

362

AN:

5262

European-Non Finnish (NFE)

AF:

0.0576

AC:

56593

AN:

982072

Other (OTH)

AF:

0.0512

AC:

2726

AN:

53214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3267

6533

9800

13066

16333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2114

4228

6342

8456

10570

<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:

0.0553

AC:

8413

AN:

152260

Hom.:

264

Cov.:

AF XY:

0.0544

AC XY:

4050

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0563

AC:

2336

AN:

41524

American (AMR)

AF:

0.0407

AC:

623

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

209

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0285

AC:

138

AN:

4834

European-Finnish (FIN)

AF:

0.0869

AC:

923

AN:

10616

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0583

AC:

3967

AN:

68014

Other (OTH)

AF:

0.0559

AC:

118

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

410

819

1229

1638

2048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0571

Hom.:

464

Bravo

AF:

0.0526

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.66

(source)

DANN

Benign

0.73

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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