10-48875066-T-C

Position:

• chr10-48875066-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.6949-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,433,968 control chromosomes in the GnomAD database, including 92,248 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 0.38 (11159 hom., cov: 33)
  • Exomes 𝑓: 0.35 (81089 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.6949-23T>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.6949-23T>C		intron_variant		5	NM_001394531.1	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57301 AN: 151954 Hom.: 11144 Cov.: 33

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.367 AC: 38069 AN: 103604 Hom.: 7512 AF XY: 0.365 AC XY: 20289 AN XY: 55556

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.733

Gnomad SAS exome AF: 0.357

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.348 AC: 446190 AN: 1281896 Hom.: 81089 Cov.: 22 AF XY: 0.348 AC XY: 219585 AN XY: 630844

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.720

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.377 AC: 57352 AN: 152072 Hom.: 11159 Cov.: 33 AF XY: 0.378 AC XY: 28127 AN XY: 74356

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.400

Alfa AF: 0.349 Hom.: 1811

Bravo AF: 0.380

Asia WGS AF: 0.497 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.81

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: rs2620881; hg19: chr10-50083111;