dbSNP rs7097397: WDFY4:p.Arg1816Gln (chr10-48817351-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.5447G>A(p.Arg1816Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,551,420 control chromosomes in the GnomAD database, including 109,799 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 9032 hom., cov: 33)

Exomes 𝑓: 0.37 ( 100767 hom. )

Consequence

WDFY4
NM_001394531.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.70

Publications

72 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 (MetaRNN=2.9394291E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1 link	c.5447G>A	p.Arg1816Gln	missense_variant	Exon 32 of 62	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12 link	c.5447G>A	p.Arg1816Gln	missense_variant	Exon 32 of 62	5	NM_001394531.1	ENSP00000320563.5		Q6ZS81-1
WDFY4	ENST00000374161.7 link	n.1086G>A		non_coding_transcript_exon_variant	Exon 9 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48707

AN:

152016

Hom.:

9033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.380

AC:

59225

AN:

155652

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.700

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.374

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.373

AC:

521972

AN:

1399286

Hom.:

100767

Cov.:

AF XY:

0.374

AC XY:

258176

AN XY:

690152

show subpopulations

African (AFR)

AF:

0.126

AC:

3968

AN:

31598

American (AMR)

AF:

0.322

AC:

11486

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

11711

AN:

25178

East Asian (EAS)

AF:

0.686

AC:

24500

AN:

35736

South Asian (SAS)

AF:

0.360

AC:

28495

AN:

79232

European-Finnish (FIN)

AF:

0.376

AC:

18507

AN:

49188

Middle Eastern (MID)

AF:

0.453

AC:

2579

AN:

5698

European-Non Finnish (NFE)

AF:

0.369

AC:

397851

AN:

1078950

Other (OTH)

AF:

0.394

AC:

22875

AN:

58004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

20427

40854

61280

81707

102134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12726

25452

38178

50904

63630

<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:

0.320

AC:

48698

AN:

152134

Hom.:

9032

Cov.:

AF XY:

0.325

AC XY:

24196

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.139

AC:

5770

AN:

41542

American (AMR)

AF:

0.346

AC:

5295

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1634

AN:

3472

East Asian (EAS)

AF:

0.690

AC:

3563

AN:

5162

South Asian (SAS)

AF:

0.377

AC:

1817

AN:

4818

European-Finnish (FIN)

AF:

0.389

AC:

4119

AN:

10580

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25195

AN:

67960

Other (OTH)

AF:

0.365

AC:

771

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1647

3293

4940

6586

8233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.365

Hom.:

20659

Bravo

AF:

0.312

TwinsUK

AF:

0.357

AC:

1322

ALSPAC

AF:

0.374

AC:

1441

ESP6500AA

AF:

0.129

AC:

179

ESP6500EA

AF:

0.389

AC:

1238

ExAC

AF:

0.343

AC:

8660

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0000029

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

PhyloP100

1.7

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.48

REVEL

Benign

0.071

Sift

Benign

0.35

Sift4G

Benign

0.066

Polyphen

0.82

Vest4

0.066

ClinPred

0.0098

GERP RS

3.6

Varity_R

0.029

gMVP

0.21

Mutation Taster

=94/6

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