NM_001394531.1:c.7524-623C>T

Variant names:

• chr10-48901178-C-T
• rs3849150
• NM_001394531.1:c.7524-623C>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.7524-623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,264 control chromosomes in the GnomAD database, including 1,514 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 0.13 (1514 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 16 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

ENSG00000241577 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.7524-623C>T		intron_variant	Intron 46 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.7524-623C>T		intron_variant	Intron 46 of 61	5	NM_001394531.1	ENSP00000320563.5
ENSG00000241577	ENST00000430438.1	n.174-16838G>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20307 AN: 152146 Hom.: 1510 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.133 AC: 20320 AN: 152264 Hom.: 1514 Cov.: 33 AF XY: 0.133 AC XY: 9918 AN XY: 74448

African (AFR) AF: 0.164 AC: 6830 AN: 41528

American (AMR) AF: 0.0995 AC: 1522 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5194

South Asian (SAS) AF: 0.166 AC: 801 AN: 4822

European-Finnish (FIN) AF: 0.140 AC: 1485 AN: 10598

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8603 AN: 68038

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.131 Hom.: 3693

Bravo AF: 0.131

Asia WGS AF: 0.0770 AC: 269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		0.12
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: rs3849150; hg19: chr10-50109223;