NM_001394531.1:c.4738+676C>T

Variant names:

• chr10-48806771-C-T
• rs2448541
• NM_001394531.1:c.4738+676C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.4738+676C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,080 control chromosomes in the GnomAD database, including 11,577 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 0.37 (11577 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 3 publications found

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]

WDFY4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.4738+676C>T		intron_variant	Intron 27 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.4738+676C>T		intron_variant	Intron 27 of 61	5	NM_001394531.1	ENSP00000320563.5
WDFY4	ENST00000374161.7	n.377+676C>T		intron_variant	Intron 4 of 12	2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55650 AN: 151962 Hom.: 11556 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.366 AC: 55713 AN: 152080 Hom.: 11577 Cov.: 33 AF XY: 0.366 AC XY: 27190 AN XY: 74338

African (AFR) AF: 0.547 AC: 22698 AN: 41474

American (AMR) AF: 0.320 AC: 4890 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3201 AN: 5180

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4812

European-Finnish (FIN) AF: 0.275 AC: 2904 AN: 10560

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18131 AN: 67984

Other (OTH) AF: 0.369 AC: 780 AN: 2112

Alfa AF: 0.272 Hom.: 3541

Bravo AF: 0.378

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.033
DANN	Benign	0.62
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2448541; hg19: chr10-50014816;