rs6537575

chr10-48771654-T-C

Variant summary

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

The NM_001394531.1(WDFY4):c.2554-2804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,192 control chromosomes in the GnomAD database, including 5,679 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 0.26 (5679 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY4	NM_001394531.1	c.2554-2804T>C		intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.2554-2804T>C		intron_variant		5	NM_001394531.1	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39242 AN: 152074 Hom.: 5664 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.258 AC: 39298 AN: 152192 Hom.: 5679 Cov.: 33 AF XY: 0.261 AC XY: 19427 AN XY: 74404

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.289

Alfa AF: 0.215 Hom.: 4857

Bravo AF: 0.262

Asia WGS AF: 0.440 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.29
Dann	Benign	0.33

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: rs6537575; hg19: chr10-49979699;