rs473664

chr15-53518798-G-A

Variant summary

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

The NM_182758.4(WDR72):c.3254-1044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,612 control chromosomes in the GnomAD database, including 17,616 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 0.48 (17616 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

LOC105370826 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.3254-1044C>T		intron_variant		ENST00000360509.10
LOC105370826	XR_007064645.1	n.388+3895G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.3254-1044C>T		intron_variant		1	NM_182758.4	P4

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72052 AN: 151490 Hom.: 17563 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.476 AC: 72180 AN: 151612 Hom.: 17616 Cov.: 32 AF XY: 0.476 AC XY: 35249 AN XY: 74046

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.480

Alfa AF: 0.429 Hom.: 22473

Bravo AF: 0.496

Asia WGS AF: 0.435 AC: 1512 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.9
Dann	Benign	0.46

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: rs473664; hg19: chr15-53810995;