rs10857636

Positions:

• chr10-48777065-C-T

Variant summary

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

The NM_001394531.1(WDFY4):​c.3098+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,420,572 control chromosomes in the GnomAD database, including 2,332 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 0.055 (264 hom., cov: 33)
  • Exomes 𝑓: 0.055 (2068 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.3098+81C>T		intron_variant		ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.3098+81C>T		intron_variant		5	NM_001394531.1	ENSP00000320563	P1

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8401 AN: 152142 Hom.: 261 Cov.: 33

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0552 AC: 70006 AN: 1268312 Hom.: 2068 AF XY: 0.0549 AC XY: 34233 AN XY: 623014

Gnomad4 AFR exome AF: 0.0581

Gnomad4 AMR exome AF: 0.0319

Gnomad4 ASJ exome AF: 0.0592

Gnomad4 EAS exome AF: 0.000115

Gnomad4 SAS exome AF: 0.0369

Gnomad4 FIN exome AF: 0.0856

Gnomad4 NFE exome AF: 0.0576

Gnomad4 OTH exome AF: 0.0512

GnomAD4 genome AF: 0.0553 AC: 8413 AN: 152260 Hom.: 264 Cov.: 33 AF XY: 0.0544 AC XY: 4050 AN XY: 74474

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0285

Gnomad4 FIN AF: 0.0869

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0581 Hom.: 257

Bravo AF: 0.0526

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10857636; hg19: chr10-49985110;