dbSNP rs2947344: WDFY4:c.2864-105G>A (chr10-48776645-G-A) – 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.2864-105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,194,218 control chromosomes in the GnomAD database, including 304,342 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 0.60 ( 30218 hom., cov: 34)

Exomes 𝑓: 0.72 ( 274124 hom. )

Consequence

WDFY4
NM_001394531.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.28

Publications

13 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 (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1 link	c.2864-105G>A		intron_variant	Intron 15 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.2864-105G>A		intron_variant	Intron 15 of 61	5	NM_001394531.1	ENSP00000320563.5		Q6ZS81-1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

91107

AN:

152080

Hom.:

30218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.701

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.738

Gnomad OTH

AF:

0.596

GnomAD4 exome

AF:

0.720

AC:

749914

AN:

1042020

Hom.:

274124

AF XY:

0.721

AC XY:

369802

AN XY:

513094

show subpopulations

African (AFR)

AF:

0.281

AC:

6601

AN:

23506

American (AMR)

AF:

0.751

AC:

14961

AN:

19924

Ashkenazi Jewish (ASJ)

AF:

0.694

AC:

12107

AN:

17456

East Asian (EAS)

AF:

0.500

AC:

16693

AN:

33370

South Asian (SAS)

AF:

0.720

AC:

41299

AN:

57336

European-Finnish (FIN)

AF:

0.715

AC:

21792

AN:

30476

Middle Eastern (MID)

AF:

0.655

AC:

2069

AN:

3160

European-Non Finnish (NFE)

AF:

0.744

AC:

603687

AN:

811436

Other (OTH)

AF:

0.677

AC:

30705

AN:

45356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9965

19929

29894

39858

49823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14230

28460

42690

56920

71150

<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:

0.599

AC:

91115

AN:

152198

Hom.:

30218

Cov.:

AF XY:

0.602

AC XY:

44773

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.300

AC:

12475

AN:

41518

American (AMR)

AF:

0.697

AC:

10667

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.694

AC:

2409

AN:

3470

East Asian (EAS)

AF:

0.498

AC:

2576

AN:

5172

South Asian (SAS)

AF:

0.699

AC:

3370

AN:

4822

European-Finnish (FIN)

AF:

0.703

AC:

7455

AN:

10598

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.738

AC:

50205

AN:

68002

Other (OTH)

AF:

0.598

AC:

1264

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1658

3316

4974

6632

8290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.694

Hom.:

167258

Bravo

AF:

0.585

Asia WGS

AF:

0.560

AC:

1951

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.083

(source)

DANN

Benign

0.55

PhyloP100

-3.3

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

Computational scores

Splicing

Publications

Other links and lift over