rs491567

chr15-53654396-A-Cchr15-53654396-A-T

Variant summary

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

The NM_182758.4(WDR72):c.1962+11176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,122 control chromosomes in the GnomAD database, including 10,718 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 0.34 (10718 hom., cov: 33)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.1962+11176T>G		intron_variant		ENST00000360509.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.1962+11176T>G		intron_variant		1	NM_182758.4	P4

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51878 AN: 152006 Hom.: 10664 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.0906

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.342 AC: 51997 AN: 152122 Hom.: 10718 Cov.: 33 AF XY: 0.346 AC XY: 25756 AN XY: 74364

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.0906

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.300

Alfa AF: 0.242 Hom.: 5778

Bravo AF: 0.357

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.4
Dann	Benign	0.82

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: rs491567; hg19: chr15-53946593;