rs76117213

Positions:

• chr4-84675083-G-A
• chr4-84675083-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014991.6(WDFY3):​c.10458-2092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 151,610 control chromosomes in the GnomAD database, including 34 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 0.019 (34 hom., cov: 31)
• Consequence: WDFY3 NM_014991.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

Genes affected

WDFY3 (HGNC:20751): (WD repeat and FYVE domain containing 3) This gene encodes a phosphatidylinositol 3-phosphate-binding protein that functions as a master conductor for aggregate clearance by autophagy. This protein shuttles from the nuclear membrane to colocalize with aggregated proteins, where it complexes with other autophagic components to achieve macroautophagy-mediated clearance of these aggregated proteins. However, it is not necessary for starvation-induced macroautophagy. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0189 (2861/151610) while in subpopulation NFE AF= 0.0268 (1820/67900). AF 95% confidence interval is 0.0258. There are 34 homozygotes in gnomad4. There are 1399 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2861 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY3	NM_014991.6	c.10458-2092C>T		intron_variant		ENST00000295888.9	NP_055806.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY3	ENST00000295888.9	c.10458-2092C>T		intron_variant		1	NM_014991.6	ENSP00000295888.4
WDFY3	ENST00000425179.2	n.1210-2092C>T		intron_variant		1
WDFY3	ENST00000514711.2	c.8898-2092C>T		intron_variant		2		ENSP00000424987.2

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2861 AN: 151492 Hom.: 34 Cov.: 31

Gnomad AFR AF: 0.00894

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00463

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00251

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0178

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

GnomAD4 genome AF: 0.0189 AC: 2861 AN: 151610 Hom.: 34 Cov.: 31 AF XY: 0.0189 AC XY: 1399 AN XY: 74010

Gnomad4 AFR AF: 0.00892

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.00463

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00251

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0176

Alfa AF: 0.0155 Hom.: 5

Bravo AF: 0.0167

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.3
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs76117213; hg19: chr4-85596236;