rs1993986

chr10-48731094-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):c.1130-16T>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
WDFY4	NM_001394531.1	c.1130-16T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.1130-16T>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001394531.1	P1
WDFY4	ENST00000360890.6	c.1130-16T>A		splice_polypyrimidine_tract_variant, intron_variant		1

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

GnomAD3 exomes AF: 0.440 AC: 56549 AN: 128612 Hom.: 12835 AF XY: 0.445 AC XY: 29813 AN XY: 66940

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 SAS exome AF: 0.477

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

Gnomad4 AFR exome AF: 0.554

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.469

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

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.507

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1993986; hg19: chr10-49939139; COSMIC: COSV57428230;