rs4332691

Positions:

• chr15-53598165-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182758.4(WDR72):​c.2953-891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,926 control chromosomes in the GnomAD database, including 7,981 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 0.29 (7981 hom., cov: 31)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

Genes affected

WDR72 (HGNC:26790): (WD repeat domain 72) This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4	c.2953-891G>A		intron_variant		ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.2953-891G>A		intron_variant		1	NM_182758.4	ENSP00000353699	P4
WDR72	ENST00000396328.5	c.2953-891G>A		intron_variant		1		ENSP00000379619	P4
WDR72	ENST00000557913.5	c.2944-891G>A		intron_variant		5		ENSP00000453378	A1
WDR72	ENST00000559418.5	c.2983-891G>A		intron_variant		5		ENSP00000452765

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44177 AN: 151808 Hom.: 7984 Cov.: 31

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.291 AC: 44164 AN: 151926 Hom.: 7981 Cov.: 31 AF XY: 0.287 AC XY: 21332 AN XY: 74234

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.326

Alfa AF: 0.393 Hom.: 22585

Bravo AF: 0.278

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.36

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: rs4332691; hg19: chr15-53890362;