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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394531.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDFY4	NM_001394531.1	MANE Select	c.3098+81C>T	intron	N/A	NP_001381460.1	Q6ZS81-1
WDFY4	NM_020945.2		c.3098+81C>T	intron	N/A	NP_065996.1	Q6ZS81-1
WDFY4	NM_001370153.1		c.3098+81C>T	intron	N/A	NP_001357082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.3098+81C>T		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.3098+81C>T		intron	N/A	ENSP00000528531.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over