Genetic Variant NM_001394531.1:c.1130-16T>A (chr10-48731094-T-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.1130-16T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,506,186 control chromosomes in the GnomAD database, including 158,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.48 ( 17645 hom., cov: 33)

Exomes 𝑓: 0.45 ( 141194 hom. )

Consequence

WDFY4
NM_001394531.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

9 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=-0.72).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 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.1130-16T>A	intron	N/A	NP_001381460.1	Q6ZS81-1
WDFY4	NM_020945.2		c.1130-16T>A	intron	N/A	NP_065996.1	Q6ZS81-1
WDFY4	NM_001370153.1		c.1130-16T>A	intron	N/A	NP_001357082.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.1130-16T>A	intron	N/A	ENSP00000320563.5	Q6ZS81-1
WDFY4	ENST00000360890.6	TSL:1	c.1130-16T>A	intron	N/A	ENSP00000354141.2	Q6ZS81-2
WDFY4	ENST00000858472.1		c.1130-16T>A	intron	N/A	ENSP00000528531.1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72251

AN:

152028

Hom.:

17640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.510

GnomAD2 exomes

AF:

0.440

AC:

56549

AN:

128612

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.473

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.454

AC:

615359

AN:

1354042

Hom.:

141194

Cov.:

AF XY:

0.456

AC XY:

301736

AN XY:

661734

show subpopulations

African (AFR)

AF:

0.554

AC:

16669

AN:

30078

American (AMR)

AF:

0.329

AC:

10046

AN:

30516

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

11178

AN:

22518

East Asian (EAS)

AF:

0.375

AC:

13161

AN:

35138

South Asian (SAS)

AF:

0.479

AC:

34641

AN:

72316

European-Finnish (FIN)

AF:

0.472

AC:

22626

AN:

47908

Middle Eastern (MID)

AF:

0.552

AC:

3021

AN:

5468

European-Non Finnish (NFE)

AF:

0.453

AC:

477772

AN:

1054192

Other (OTH)

AF:

0.469

AC:

26245

AN:

55908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

18149

36297

54446

72594

90743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14852

29704

44556

59408

74260

<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:

0.475

AC:

72291

AN:

152144

Hom.:

17645

Cov.:

AF XY:

0.475

AC XY:

35320

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.545

AC:

22595

AN:

41492

American (AMR)

AF:

0.401

AC:

6126

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1776

AN:

3470

East Asian (EAS)

AF:

0.362

AC:

1875

AN:

5180

South Asian (SAS)

AF:

0.483

AC:

2334

AN:

4828

European-Finnish (FIN)

AF:

0.475

AC:

5020

AN:

10578

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.455

AC:

30965

AN:

67984

Other (OTH)

AF:

0.507

AC:

1072

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1933

3866

5798

7731

9664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.466

Hom.:

3064

Bravo

AF:

0.470

Asia WGS

AF:

0.423

AC:

1476

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.9

(source)

DANN

Benign

0.79

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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