chr10-48837411-T-G

Variant names:

• chr10-48837411-T-G
• rs7922169
• NM_001394531.1:c.6663+4702T>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+4702T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,892 control chromosomes in the GnomAD database, including 22,332 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 0.53 (22332 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.49
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.6663+4702T>G		intron_variant	Intron 39 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.6663+4702T>G		intron_variant	Intron 39 of 61	5	NM_001394531.1	ENSP00000320563.5
ENSG00000286993	ENST00000664118.1	n.104-454A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80569 AN: 151774 Hom.: 22307 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.531 AC: 80641 AN: 151892 Hom.: 22332 Cov.: 33 AF XY: 0.530 AC XY: 39358 AN XY: 74200

African (AFR) AF: 0.683 AC: 28317 AN: 41448

American (AMR) AF: 0.463 AC: 7071 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1822 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3645 AN: 5148

South Asian (SAS) AF: 0.509 AC: 2451 AN: 4816

European-Finnish (FIN) AF: 0.474 AC: 4983 AN: 10508

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30561 AN: 67916

Other (OTH) AF: 0.543 AC: 1143 AN: 2106

Alfa AF: 0.472 Hom.: 9869

Bravo AF: 0.538

Asia WGS AF: 0.560 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.55
PhyloP100		-4.5
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: rs7922169; hg19: chr10-50045456;