dbSNP rs10857625: WDFY4:c.456+79A>C (chr10-48721446-A-C) – 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.456+79A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,307,158 control chromosomes in the GnomAD database, including 121,258 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 0.40 ( 13019 hom., cov: 31)

Exomes 𝑓: 0.43 ( 108239 hom. )

Consequence

WDFY4
NM_001394531.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

5 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 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
WDFY4	NM_001394531.1	MANE Select	c.456+79A>C	intron	N/A	NP_001381460.1
WDFY4	NM_020945.2		c.456+79A>C	intron	N/A	NP_065996.1
WDFY4	NM_001370153.1		c.456+79A>C	intron	N/A	NP_001357082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.456+79A>C		intron	N/A	ENSP00000320563.5
	WDFY4	ENST00000360890.6	TSL:1	c.456+79A>C		intron	N/A	ENSP00000354141.2

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61124

AN:

151760

Hom.:

13007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.750

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.426

AC:

492202

AN:

1155280

Hom.:

108239

AF XY:

0.425

AC XY:

246012

AN XY:

578854

show subpopulations

African (AFR)

AF:

0.329

AC:

8715

AN:

26514

American (AMR)

AF:

0.622

AC:

21894

AN:

35212

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6172

AN:

23366

East Asian (EAS)

AF:

0.758

AC:

26212

AN:

34600

South Asian (SAS)

AF:

0.447

AC:

33162

AN:

74270

European-Finnish (FIN)

AF:

0.431

AC:

21111

AN:

48972

Middle Eastern (MID)

AF:

0.254

AC:

1313

AN:

5166

European-Non Finnish (NFE)

AF:

0.412

AC:

353232

AN:

857328

Other (OTH)

AF:

0.409

AC:

20391

AN:

49852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

13716

27431

41147

54862

68578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10394

20788

31182

41576

51970

<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:

0.403

AC:

61177

AN:

151878

Hom.:

13019

Cov.:

AF XY:

0.407

AC XY:

30207

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.337

AC:

13950

AN:

41406

American (AMR)

AF:

0.485

AC:

7410

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

915

AN:

3468

East Asian (EAS)

AF:

0.750

AC:

3857

AN:

5146

South Asian (SAS)

AF:

0.457

AC:

2195

AN:

4802

European-Finnish (FIN)

AF:

0.446

AC:

4698

AN:

10530

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26928

AN:

67930

Other (OTH)

AF:

0.359

AC:

756

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1789

3578

5367

7156

8945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.404

Hom.:

19570

Bravo

AF:

0.408

Asia WGS

AF:

0.560

AC:

1947

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.026

(source)

DANN

Benign

0.72

PhyloP100

-1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over