rs7168365

Variant names:

• chr15-53513628-C-A
• rs7168365
• ENST00000851014.1:n.467-376C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-53513628-C-A
• chr15-53513628-C-G

Variant summary

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

The ENST00000851014.1(ENSG00000287596):​n.467-376C>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: ENSG00000287596 ENST00000851014.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 10 publications found

Genes affected

ENSG00000287596 (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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000851014.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	NM_182758.4	MANE Select	c.*4071G>T		downstream_gene	N/A	NP_877435.3	Q3MJ13
	WDR72	NM_001277176.2		c.*4071G>T		downstream_gene	N/A	NP_001264105.1	A0A087WTC3
	WDR72	NR_102334.2		n.*113G>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000287596	ENST00000851014.1		n.467-376C>A		intron	N/A
	ENSG00000287596	ENST00000851015.1		n.172-376C>A		intron	N/A
	WDR72	ENST00000360509.10	TSL:1 MANE Select	c.*4071G>T		downstream_gene	N/A	ENSP00000353699.5	Q3MJ13

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7168365;

hg19: chr15-53805825;