chr10-48834274-A-G

Variant names:

• chr10-48834274-A-G
• rs735104
• NM_001394531.1:c.6663+1565A>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+1565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,982 control chromosomes in the GnomAD database, including 15,537 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 0.44 (15537 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 0 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=-0.85).
• 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+1565A>G		intron	N/A	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.6663+1565A>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+1565A>G		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.6663+1565A>G		intron	N/A	ENSP00000528531.1
	ENSG00000286993	ENST00000760415.1		n.262-6T>C		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66691 AN: 151864 Hom.: 15519 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.439 AC: 66750 AN: 151982 Hom.: 15537 Cov.: 32 AF XY: 0.441 AC XY: 32759 AN XY: 74286

African (AFR) AF: 0.530 AC: 21967 AN: 41436

American (AMR) AF: 0.430 AC: 6564 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4286 AN: 5172

South Asian (SAS) AF: 0.468 AC: 2253 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4020 AN: 10544

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

European-Non Finnish (NFE) AF: 0.366 AC: 24901 AN: 67952

Other (OTH) AF: 0.448 AC: 947 AN: 2112

Alfa AF: 0.399 Hom.: 1604

Bravo AF: 0.446

Asia WGS AF: 0.609 AC: 2118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		0.27
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: rs735104; hg19: chr10-50042319;