rs2663049

Positions:

• chr10-48858716-G-A
• chr10-48858716-G-C
• chr10-48858716-G-T

Variant summary

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

The NM_001394531.1(WDFY4):​c.6664-8549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,940 control chromosomes in the GnomAD database, including 16,535 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 0.44 (16535 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY4	NM_001394531.1	c.6664-8549G>A		intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.6664-8549G>A		intron_variant		5	NM_001394531.1	P1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67468 AN: 151822 Hom.: 16511 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.445 AC: 67542 AN: 151940 Hom.: 16535 Cov.: 32 AF XY: 0.443 AC XY: 32887 AN XY: 74212

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.447

Alfa AF: 0.325 Hom.: 3675

Bravo AF: 0.457

Asia WGS AF: 0.499 AC: 1738 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.22

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: rs2663049; hg19: chr10-50066761;