rs10857625

Positions:

• chr10-48721446-A-C
• chr10-48721446-A-G

Variant summary

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

The NM_001394531.1(WDFY4):​c.456+79A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,307,158 control chromosomes in the GnomAD database, including 121,258 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 0.40 (13019 hom., cov: 31)
  • Exomes 𝑓: 0.43 (108239 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.456+79A>C		intron_variant		ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.456+79A>C		intron_variant		5	NM_001394531.1	ENSP00000320563	P1
WDFY4	ENST00000360890.6	c.456+79A>C		intron_variant		1		ENSP00000354141

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61124 AN: 151760 Hom.: 13007 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.426 AC: 492202 AN: 1155280 Hom.: 108239 AF XY: 0.425 AC XY: 246012 AN XY: 578854

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.403 AC: 61177 AN: 151878 Hom.: 13019 Cov.: 31 AF XY: 0.407 AC XY: 30207 AN XY: 74212

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.359

Alfa AF: 0.393 Hom.: 2544

Bravo AF: 0.408

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.026
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs10857625; hg19: chr10-49929491;