Genetic Variant 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.

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.2864-105G>A	intron	N/A	NP_001381460.1	Q6ZS81-1
WDFY4	NM_020945.2		c.2864-105G>A	intron	N/A	NP_065996.1	Q6ZS81-1
WDFY4	NM_001370153.1		c.2864-105G>A	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.2864-105G>A		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.2864-105G>A		intron	N/A	ENSP00000528531.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over