NM_001394531.1:c.457-329G>A

Variant names:

• chr10-48723104-G-A
• rs10508906
• NM_001394531.1:c.457-329G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.457-329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 151,798 control chromosomes in the GnomAD database, including 44,203 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 0.76 (44203 hom., cov: 28)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 3 publications found

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

ACMG classification

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 = 0.852 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.457-329G>A		intron	N/A	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.457-329G>A		intron	N/A	NP_065996.1	Q6ZS81-1
	WDFY4	NM_001370153.1		c.457-329G>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.457-329G>A		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000360890.6	TSL:1	c.457-329G>A		intron	N/A	ENSP00000354141.2	Q6ZS81-2
	WDFY4	ENST00000858472.1		c.457-329G>A		intron	N/A	ENSP00000528531.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115381 AN: 151680 Hom.: 44169 Cov.: 28

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.740

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.761 AC: 115468 AN: 151798 Hom.: 44203 Cov.: 28 AF XY: 0.764 AC XY: 56678 AN XY: 74180

African (AFR) AF: 0.804 AC: 33247 AN: 41350

American (AMR) AF: 0.754 AC: 11503 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2211 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4500 AN: 5152

South Asian (SAS) AF: 0.860 AC: 4135 AN: 4808

European-Finnish (FIN) AF: 0.798 AC: 8417 AN: 10542

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48984 AN: 67906

Other (OTH) AF: 0.736 AC: 1545 AN: 2100

Alfa AF: 0.727 Hom.: 63344

Bravo AF: 0.759

Asia WGS AF: 0.813 AC: 2826 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	0.28
DANN	Benign	0.22
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10508906; hg19: chr10-49931149;