NM_001394531.1:c.2554-6437C>A

Variant names:

• chr10-48768021-C-A
• rs17011183
• NM_001394531.1:c.2554-6437C>A

Variant summary

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

The NM_001394531.1(WDFY4):​c.2554-6437C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,142 control chromosomes in the GnomAD database, including 635 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 0.082 (635 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.2554-6437C>A		intron_variant	Intron 13 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.2554-6437C>A		intron_variant	Intron 13 of 61	5	NM_001394531.1	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12454 AN: 152024 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.0820 AC: 12482 AN: 152142 Hom.: 635 Cov.: 32 AF XY: 0.0839 AC XY: 6237 AN XY: 74382

African (AFR) AF: 0.114 AC: 4712 AN: 41490

American (AMR) AF: 0.0703 AC: 1075 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3472

East Asian (EAS) AF: 0.138 AC: 716 AN: 5180

South Asian (SAS) AF: 0.112 AC: 541 AN: 4810

European-Finnish (FIN) AF: 0.0666 AC: 706 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4153 AN: 67990

Other (OTH) AF: 0.0930 AC: 196 AN: 2108

Alfa AF: 0.0750 Hom.: 179

Bravo AF: 0.0839

Asia WGS AF: 0.134 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		0.30
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: rs17011183; hg19: chr10-49976066;