rs2271565

Variant names:

• chr10-48976904-C-T
• rs2271565
• NM_001394531.1:c.9216C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6 BP7 BA1

The NM_001394531.1(WDFY4):​c.9216C>T​(p.Cys3072Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,537,308 control chromosomes in the GnomAD database, including 179,851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (12696 hom., cov: 33)
  • Exomes 𝑓: 0.48 (167155 hom.)
• Consequence: WDFY4 NM_001394531.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.41
• Publications: 16 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

ENSG00000233665 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.186).
• BP6: Variant 10-48976904-C-T is Benign according to our data. Variant chr10-48976904-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059895.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 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.9216C>T	p.Cys3072Cys	synonymous	Exon 59 of 62	NP_001381460.1
	WDFY4	NM_020945.2		c.9216C>T	p.Cys3072Cys	synonymous	Exon 59 of 62	NP_065996.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.9216C>T	p.Cys3072Cys	synonymous	Exon 59 of 62	ENSP00000320563.5
	ENSG00000233665	ENST00000428825.8	TSL:5	n.1260G>A		non_coding_transcript_exon	Exon 5 of 5
	WDFY4	ENST00000465910.5	TSL:2	n.3850C>T		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57128 AN: 152060 Hom.: 12696 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.380

GnomAD2 exomes AF: 0.429 AC: 62188 AN: 144972 AF XY: 0.438

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.314

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.484 AC: 670985 AN: 1385130 Hom.: 167155 Cov.: 53 AF XY: 0.484 AC XY: 330760 AN XY: 682862

African (AFR) AF: 0.106 AC: 3290 AN: 31084

American (AMR) AF: 0.385 AC: 13146 AN: 34158

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 10484 AN: 24828

East Asian (EAS) AF: 0.249 AC: 8647 AN: 34692

South Asian (SAS) AF: 0.470 AC: 36338 AN: 77234

European-Finnish (FIN) AF: 0.424 AC: 20805 AN: 49032

Middle Eastern (MID) AF: 0.394 AC: 2221 AN: 5644

European-Non Finnish (NFE) AF: 0.513 AC: 549826 AN: 1071090

Other (OTH) AF: 0.457 AC: 26228 AN: 57368

GnomAD4 genome AF: 0.375 AC: 57130 AN: 152178 Hom.: 12696 Cov.: 33 AF XY: 0.375 AC XY: 27866 AN XY: 74376

African (AFR) AF: 0.129 AC: 5343 AN: 41554

American (AMR) AF: 0.402 AC: 6145 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1444 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1661 AN: 5160

South Asian (SAS) AF: 0.474 AC: 2284 AN: 4814

European-Finnish (FIN) AF: 0.408 AC: 4325 AN: 10600

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34550 AN: 67968

Other (OTH) AF: 0.384 AC: 812 AN: 2112

Alfa AF: 0.451 Hom.: 13267

Bravo AF: 0.361

Asia WGS AF: 0.427 AC: 1480 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	WDFY4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		1.4
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: rs2271565; hg19: chr10-50184949; COSMIC: COSV55424782; COSMIC: COSV55424782;