rs1993986

Variant names:

• chr10-48731094-T-A
• rs1993986
• NM_001394531.1:c.1130-16T>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.1130-16T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,506,186 control chromosomes in the GnomAD database, including 158,839 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 0.48 (17645 hom., cov: 33)
  • Exomes 𝑓: 0.45 (141194 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 9 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.1130-16T>A		intron_variant	Intron 8 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.1130-16T>A		intron_variant	Intron 8 of 61	5	NM_001394531.1	ENSP00000320563.5
WDFY4	ENST00000360890.6	c.1130-16T>A		intron_variant	Intron 8 of 10	1		ENSP00000354141.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72251 AN: 152028 Hom.: 17640 Cov.: 33

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.510

GnomAD2 exomes AF: 0.440 AC: 56549 AN: 128612 AF XY: 0.445

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.359

Gnomad FIN exome AF: 0.473

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.454 AC: 615359 AN: 1354042 Hom.: 141194 Cov.: 32 AF XY: 0.456 AC XY: 301736 AN XY: 661734

African (AFR) AF: 0.554 AC: 16669 AN: 30078

American (AMR) AF: 0.329 AC: 10046 AN: 30516

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 11178 AN: 22518

East Asian (EAS) AF: 0.375 AC: 13161 AN: 35138

South Asian (SAS) AF: 0.479 AC: 34641 AN: 72316

European-Finnish (FIN) AF: 0.472 AC: 22626 AN: 47908

Middle Eastern (MID) AF: 0.552 AC: 3021 AN: 5468

European-Non Finnish (NFE) AF: 0.453 AC: 477772 AN: 1054192

Other (OTH) AF: 0.469 AC: 26245 AN: 55908

GnomAD4 genome AF: 0.475 AC: 72291 AN: 152144 Hom.: 17645 Cov.: 33 AF XY: 0.475 AC XY: 35320 AN XY: 74372

African (AFR) AF: 0.545 AC: 22595 AN: 41492

American (AMR) AF: 0.401 AC: 6126 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1875 AN: 5180

South Asian (SAS) AF: 0.483 AC: 2334 AN: 4828

European-Finnish (FIN) AF: 0.475 AC: 5020 AN: 10578

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30965 AN: 67984

Other (OTH) AF: 0.507 AC: 1072 AN: 2114

Alfa AF: 0.466 Hom.: 3064

Bravo AF: 0.470

Asia WGS AF: 0.423 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Benign	0.79
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1993986; hg19: chr10-49939139; COSMIC: COSV57428230;