10-48875066-T-C

Variant names:

• chr10-48875066-T-C
• rs2620881
• NM_001394531.1:c.6949-23T>C

Variant summary

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

The NM_001394531.1(WDFY4):​c.6949-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,433,968 control chromosomes in the GnomAD database, including 92,248 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 0.38 (11159 hom., cov: 33)
  • Exomes 𝑓: 0.35 (81089 hom.)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• Publications: 13 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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.6949-23T>C		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.6949-23T>C		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.6949-23T>C		intron	N/A	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57301 AN: 151954 Hom.: 11144 Cov.: 33

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.367 AC: 38069 AN: 103604 AF XY: 0.365

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.733

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.348 AC: 446190 AN: 1281896 Hom.: 81089 Cov.: 22 AF XY: 0.348 AC XY: 219585 AN XY: 630844

African (AFR) AF: 0.415 AC: 11144 AN: 26884

American (AMR) AF: 0.346 AC: 7740 AN: 22358

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 7422 AN: 22402

East Asian (EAS) AF: 0.720 AC: 22360 AN: 31054

South Asian (SAS) AF: 0.352 AC: 21207 AN: 60240

European-Finnish (FIN) AF: 0.352 AC: 16442 AN: 46772

Middle Eastern (MID) AF: 0.356 AC: 1913 AN: 5370

European-Non Finnish (NFE) AF: 0.333 AC: 338013 AN: 1013866

Other (OTH) AF: 0.377 AC: 19949 AN: 52950

GnomAD4 genome AF: 0.377 AC: 57352 AN: 152072 Hom.: 11159 Cov.: 33 AF XY: 0.378 AC XY: 28127 AN XY: 74356

African (AFR) AF: 0.407 AC: 16875 AN: 41446

American (AMR) AF: 0.368 AC: 5619 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3470

East Asian (EAS) AF: 0.712 AC: 3688 AN: 5182

South Asian (SAS) AF: 0.385 AC: 1860 AN: 4830

European-Finnish (FIN) AF: 0.363 AC: 3840 AN: 10568

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22969 AN: 67980

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.355 Hom.: 13541

Bravo AF: 0.380

Asia WGS AF: 0.497 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2620881; hg19: chr10-50083111;