rs11595065

Variant names:

• chr10-48769837-G-A
• rs11595065
• NM_001394531.1:c.2554-4621G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-48769837-G-A
• chr10-48769837-G-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.2554-4621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,086 control chromosomes in the GnomAD database, including 15,472 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 0.45 (15472 hom., cov: 33)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• 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 = 0.513 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.2554-4621G>A		intron	N/A	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.2554-4621G>A		intron	N/A	NP_065996.1	Q6ZS81-1
	WDFY4	NM_001370153.1		c.2554-4621G>A		intron	N/A	NP_001357082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.2554-4621G>A		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.2554-4621G>A		intron	N/A	ENSP00000528531.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68156 AN: 151968 Hom.: 15461 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.448 AC: 68208 AN: 152086 Hom.: 15472 Cov.: 33 AF XY: 0.450 AC XY: 33458 AN XY: 74344

African (AFR) AF: 0.431 AC: 17862 AN: 41488

American (AMR) AF: 0.430 AC: 6568 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2735 AN: 5162

South Asian (SAS) AF: 0.466 AC: 2244 AN: 4818

European-Finnish (FIN) AF: 0.448 AC: 4739 AN: 10576

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30355 AN: 67970

Other (OTH) AF: 0.499 AC: 1053 AN: 2112

Alfa AF: 0.447 Hom.: 52503

Bravo AF: 0.445

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.73
PhyloP100		-0.36
Mutation Taster		=99/1	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: rs11595065; hg19: chr10-49977882;