15-53513628-C-A

Variant names:

• chr15-53513628-C-A
• rs7168365
• XR_007064643.1:n.167-376C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007064643.1(LOC105370826):​n.167-376C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,852 control chromosomes in the GnomAD database, including 11,147 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 0.37 (11147 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LOC105370826 XR_007064643.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 10 publications found

Genes affected

LOC105370826 (HGNC:):

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.*4071G>T		downstream_gene_variant		ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.*4071G>T		downstream_gene_variant		1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328.5	c.*4071G>T		downstream_gene_variant		1		ENSP00000379619.1
WDR72	ENST00000567224.1	n.*113G>T		downstream_gene_variant		1
WDR72	ENST00000614174.4	c.*4071G>T		downstream_gene_variant		2		ENSP00000477754.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56829 AN: 151734 Hom.: 11134 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.375 AC: 56884 AN: 151852 Hom.: 11147 Cov.: 32 AF XY: 0.377 AC XY: 27966 AN XY: 74218

African (AFR) AF: 0.267 AC: 11069 AN: 41388

American (AMR) AF: 0.491 AC: 7484 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1448 AN: 3466

East Asian (EAS) AF: 0.390 AC: 2002 AN: 5132

South Asian (SAS) AF: 0.435 AC: 2094 AN: 4810

European-Finnish (FIN) AF: 0.363 AC: 3828 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27514 AN: 67938

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.396 Hom.: 25038

Bravo AF: 0.382

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.085

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7168365; hg19: chr15-53805825;