rs7097397

Variant names:

• chr10-48817351-G-A
• rs7097397
• NM_001394531.1:c.5447G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-48817351-G-A
• chr10-48817351-G-C
• chr10-48817351-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.5447G>A​(p.Arg1816Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,551,420 control chromosomes in the GnomAD database, including 109,799 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9032 hom., cov: 33)
  • Exomes 𝑓: 0.37 (100767 hom.)
• Consequence: WDFY4 NM_001394531.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 72 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 (MetaRNN=2.9394291E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 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.5447G>A	p.Arg1816Gln	missense	Exon 32 of 62	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.5447G>A	p.Arg1816Gln	missense	Exon 32 of 62	NP_065996.1	Q6ZS81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.5447G>A	p.Arg1816Gln	missense	Exon 32 of 62	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.5447G>A	p.Arg1816Gln	missense	Exon 32 of 62	ENSP00000528531.1
	WDFY4	ENST00000374161.7	TSL:2	n.1086G>A		non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48707 AN: 152016 Hom.: 9033 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.380 AC: 59225 AN: 155652 AF XY: 0.383

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.700

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.373 AC: 521972 AN: 1399286 Hom.: 100767 Cov.: 58 AF XY: 0.374 AC XY: 258176 AN XY: 690152

African (AFR) AF: 0.126 AC: 3968 AN: 31598

American (AMR) AF: 0.322 AC: 11486 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 11711 AN: 25178

East Asian (EAS) AF: 0.686 AC: 24500 AN: 35736

South Asian (SAS) AF: 0.360 AC: 28495 AN: 79232

European-Finnish (FIN) AF: 0.376 AC: 18507 AN: 49188

Middle Eastern (MID) AF: 0.453 AC: 2579 AN: 5698

European-Non Finnish (NFE) AF: 0.369 AC: 397851 AN: 1078950

Other (OTH) AF: 0.394 AC: 22875 AN: 58004

GnomAD4 genome AF: 0.320 AC: 48698 AN: 152134 Hom.: 9032 Cov.: 33 AF XY: 0.325 AC XY: 24196 AN XY: 74372

African (AFR) AF: 0.139 AC: 5770 AN: 41542

American (AMR) AF: 0.346 AC: 5295 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3563 AN: 5162

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4818

European-Finnish (FIN) AF: 0.389 AC: 4119 AN: 10580

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25195 AN: 67960

Other (OTH) AF: 0.365 AC: 771 AN: 2114

Alfa AF: 0.365 Hom.: 20659

Bravo AF: 0.312

TwinsUK AF: 0.357 AC: 1322

ALSPAC AF: 0.374 AC: 1441

ESP6500AA AF: 0.129 AC: 179

ESP6500EA AF: 0.389 AC: 1238

ExAC AF: 0.343 AC: 8660

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0000029	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.071
Sift	Benign	0.35	T
Sift4G	Benign	0.066	T
Polyphen		0.82	P
Vest4		0.066
ClinPred		0.0098	T
GERP RS		3.6
Varity_R		0.029
gMVP		0.21
Mutation Taster		=94/6	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: rs7097397; hg19: chr10-50025396; COSMIC: COSV55431993;