10-48723570-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001394531.1(WDFY4):c.591+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,551,792 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (123 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (113 hom.)
• Consequence: WDFY4 NM_001394531.1 splice_donor_region, intron
• Scores: Splicing: ADA: 0.001357
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 10-48723570-G-A is Benign according to our data. Variant chr10-48723570-G-A is described in ClinVar as [Benign]. Clinvar id is 785317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY4	NM_001394531.1	c.591+3G>A		splice_donor_region_variant, intron_variant		ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.591+3G>A		splice_donor_region_variant, intron_variant		5	NM_001394531.1	P1
WDFY4	ENST00000360890.6	c.591+3G>A		splice_donor_region_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3385 AN: 152140 Hom.: 123 Cov.: 31

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00527 AC: 831 AN: 157656 Hom.: 18 AF XY: 0.00418 AC XY: 348 AN XY: 83284

Gnomad AFR exome AF: 0.0798

Gnomad AMR exome AF: 0.00523

Gnomad ASJ exome AF: 0.000823

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000176

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00471

GnomAD4 exome AF: 0.00244 AC: 3413 AN: 1399534 Hom.: 113 Cov.: 31 AF XY: 0.00217 AC XY: 1498 AN XY: 690260

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.00588

Gnomad4 ASJ exome AF: 0.000437

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.0000202

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.00553

GnomAD4 genome AF: 0.0223 AC: 3391 AN: 152258 Hom.: 123 Cov.: 31 AF XY: 0.0218 AC XY: 1623 AN XY: 74436

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0150 Hom.: 36

Bravo AF: 0.0258

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	16
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.016
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

Publications

LitVar

Other links and lift over

dbSNP: rs111563360; hg19: chr10-49931615;