10-48975692-T-C

Variant names:

• chr10-48975692-T-C
• rs1317894
• NM_001394531.1:c.9108+651T>C

Variant summary

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

The NM_001394531.1(WDFY4):​c.9108+651T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,062 control chromosomes in the GnomAD database, including 54,645 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 0.83 (54645 hom., cov: 31)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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.9108+651T>C		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.9108+651T>C		intron	N/A	NP_065996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.9108+651T>C		intron	N/A	ENSP00000320563.5
	WDFY4	ENST00000465910.5	TSL:2	n.3742+651T>C		intron	N/A
	WDFY4	ENST00000497480.1	TSL:2	n.604+651T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126730 AN: 151944 Hom.: 54642 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.834 AC: 126768 AN: 152062 Hom.: 54645 Cov.: 31 AF XY: 0.836 AC XY: 62168 AN XY: 74344

African (AFR) AF: 0.589 AC: 24383 AN: 41374

American (AMR) AF: 0.884 AC: 13521 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3058 AN: 3468

East Asian (EAS) AF: 0.976 AC: 5054 AN: 5178

South Asian (SAS) AF: 0.889 AC: 4282 AN: 4818

European-Finnish (FIN) AF: 0.944 AC: 10004 AN: 10596

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63604 AN: 68018

Other (OTH) AF: 0.847 AC: 1792 AN: 2116

Alfa AF: 0.902 Hom.: 37869

Bravo AF: 0.818

Asia WGS AF: 0.906 AC: 3151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.72
PhyloP100		0.55
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: rs1317894; hg19: chr10-50183737;