10-48889774-G-A

Variant names:

• chr10-48889774-G-A
• rs2671692
• NM_001394531.1:c.7168-805G>A

Variant summary

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

The NM_001394531.1(WDFY4):​c.7168-805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,070 control chromosomes in the GnomAD database, including 23,040 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 0.54 (23040 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 32 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

ENSG00000241577 (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 (NFE) allele frequency at 95% confidence interval = 0.62 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.7168-805G>A		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.7168-805G>A		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.7168-805G>A		intron	N/A	ENSP00000320563.5
	ENSG00000241577	ENST00000430438.1	TSL:5	n.174-5434C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82061 AN: 151952 Hom.: 23013 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.540 AC: 82138 AN: 152070 Hom.: 23040 Cov.: 33 AF XY: 0.536 AC XY: 39850 AN XY: 74340

African (AFR) AF: 0.418 AC: 17331 AN: 41460

American (AMR) AF: 0.579 AC: 8846 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1481 AN: 5172

South Asian (SAS) AF: 0.466 AC: 2249 AN: 4822

European-Finnish (FIN) AF: 0.594 AC: 6275 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42458 AN: 67978

Other (OTH) AF: 0.514 AC: 1086 AN: 2112

Alfa AF: 0.587 Hom.: 81403

Bravo AF: 0.534

Asia WGS AF: 0.426 AC: 1479 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	1.3
DANN	Benign	0.69
PhyloP100		0.22
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: rs2671692; hg19: chr10-50097819;