chr10-48738221-A-G

Variant names:

• chr10-48738221-A-G
• rs17698900
• NM_001394531.1:c.1878+2151A>G

Variant summary

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

The ENST00000325239.12(WDFY4):​c.1878+2151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,252 control chromosomes in the GnomAD database, including 759 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 0.092 (759 hom., cov: 33)
• Consequence: WDFY4 ENST00000325239.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325239.12. 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.1878+2151A>G		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.1878+2151A>G		intron	N/A	NP_065996.1
	WDFY4	NM_001370153.1		c.1878+2151A>G		intron	N/A	NP_001357082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.1878+2151A>G		intron	N/A	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14070 AN: 152134 Hom.: 760 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0924 AC: 14069 AN: 152252 Hom.: 759 Cov.: 33 AF XY: 0.0885 AC XY: 6589 AN XY: 74440

African (AFR) AF: 0.0557 AC: 2314 AN: 41542

American (AMR) AF: 0.0912 AC: 1397 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0449 AC: 216 AN: 4816

European-Finnish (FIN) AF: 0.0970 AC: 1028 AN: 10602

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8359 AN: 68010

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.101 Hom.: 110

Bravo AF: 0.0912

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.56
PhyloP100		-1.9
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: rs17698900; hg19: chr10-49946266;