10-48834906-A-G

Variant names:

• chr10-48834906-A-G
• rs877819
• NM_001394531.1:c.6663+2197A>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.6663+2197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,090 control chromosomes in the GnomAD database, including 16,255 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 0.45 (16255 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 29 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

ENSG00000286993 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 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.6663+2197A>G		intron	N/A	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.6663+2197A>G		intron	N/A	NP_065996.1	Q6ZS81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.6663+2197A>G		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.6663+2197A>G		intron	N/A	ENSP00000528531.1
	ENSG00000286993	ENST00000760415.1		n.261+196T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68066 AN: 151972 Hom.: 16229 Cov.: 33

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.448 AC: 68141 AN: 152090 Hom.: 16255 Cov.: 33 AF XY: 0.449 AC XY: 33403 AN XY: 74360

African (AFR) AF: 0.561 AC: 23273 AN: 41496

American (AMR) AF: 0.434 AC: 6642 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3466

East Asian (EAS) AF: 0.829 AC: 4273 AN: 5154

South Asian (SAS) AF: 0.468 AC: 2260 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4021 AN: 10578

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24898 AN: 67956

Other (OTH) AF: 0.456 AC: 964 AN: 2116

Alfa AF: 0.394 Hom.: 23428

Bravo AF: 0.457

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.34
PhyloP100		-0.65
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: rs877819; hg19: chr10-50042951;