rs4332691

Variant names:

• chr15-53598165-C-T
• rs4332691
• NM_182758.4:c.2953-891G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

WDR72 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• amelogenesis imperfecta hypomaturation type 2A3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal tubular acidosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.2953-891G>A		intron_variant	Intron 17 of 19	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.2953-891G>A		intron_variant	Intron 17 of 19	1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328.5	c.2953-891G>A		intron_variant	Intron 17 of 19	1		ENSP00000379619.1
WDR72	ENST00000559418.5	c.2983-891G>A		intron_variant	Intron 16 of 18	5		ENSP00000452765.1
WDR72	ENST00000557913.5	c.2944-891G>A		intron_variant	Intron 17 of 19	5		ENSP00000453378.1

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

African (AFR) AF: 0.0856 AC: 3549 AN: 41460

American (AMR) AF: 0.283 AC: 4323 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1959 AN: 3472

East Asian (EAS) AF: 0.192 AC: 986 AN: 5130

South Asian (SAS) AF: 0.437 AC: 2092 AN: 4788

European-Finnish (FIN) AF: 0.286 AC: 3020 AN: 10554

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26889 AN: 67960

Other (OTH) AF: 0.326 AC: 685 AN: 2102

Alfa AF: 0.369 Hom.: 33667

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
PhyloP100		-0.68
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: rs4332691; hg19: chr15-53890362;