10-48852457-G-A

Variant names:

• chr10-48852457-G-A
• rs2620887
• NM_001394531.1:c.6664-14808G>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.6664-14808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,046 control chromosomes in the GnomAD database, including 10,717 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 (10717 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394531.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.6664-14808G>A		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.6664-14808G>A		intron	N/A	NP_065996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.6664-14808G>A		intron	N/A	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56085 AN: 151928 Hom.: 10704 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.369 AC: 56129 AN: 152046 Hom.: 10717 Cov.: 32 AF XY: 0.371 AC XY: 27575 AN XY: 74318

African (AFR) AF: 0.386 AC: 16011 AN: 41476

American (AMR) AF: 0.364 AC: 5561 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1153 AN: 3466

East Asian (EAS) AF: 0.706 AC: 3644 AN: 5160

South Asian (SAS) AF: 0.376 AC: 1812 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3840 AN: 10560

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22787 AN: 67960

Other (OTH) AF: 0.396 AC: 835 AN: 2110

Alfa AF: 0.349 Hom.: 1602

Bravo AF: 0.372

Asia WGS AF: 0.486 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		-0.16
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: rs2620887; hg19: chr10-50060502;