10-48807166-T-G

Variant names:

• chr10-48807166-T-G
• rs2448539
• NM_001394531.1:c.4739-693T>G

Variant summary

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

The NM_001394531.1(WDFY4):​c.4739-693T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,978 control chromosomes in the GnomAD database, including 24,229 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 0.56 (24229 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.4739-693T>G		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.4739-693T>G		intron	N/A	NP_065996.1
	WDFY4	NM_001370153.1		c.4739-693T>G		intron	N/A	NP_001357082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.4739-693T>G		intron	N/A	ENSP00000320563.5
	WDFY4	ENST00000374161.7	TSL:2	n.378-693T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84813 AN: 151860 Hom.: 24198 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.559 AC: 84902 AN: 151978 Hom.: 24229 Cov.: 32 AF XY: 0.559 AC XY: 41549 AN XY: 74286

African (AFR) AF: 0.646 AC: 26784 AN: 41438

American (AMR) AF: 0.522 AC: 7972 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3470

East Asian (EAS) AF: 0.830 AC: 4287 AN: 5164

South Asian (SAS) AF: 0.592 AC: 2851 AN: 4818

European-Finnish (FIN) AF: 0.524 AC: 5525 AN: 10548

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33678 AN: 67954

Other (OTH) AF: 0.568 AC: 1194 AN: 2102

Alfa AF: 0.493 Hom.: 9092

Bravo AF: 0.563

Asia WGS AF: 0.658 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.19
PhyloP100		0.077
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: rs2448539; hg19: chr10-50015211;