rs12936231

Positions:

• chr17-39872867-C-G
• chr17-39872867-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000348931.9(ZPBP2):​c.626-177C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,030 control chromosomes in the GnomAD database, including 19,088 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 0.50 (19088 hom., cov: 32)
• Consequence: ZPBP2 ENST00000348931.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11

Genes affected

ZPBP2 (HGNC:20678): (zona pellucida binding protein 2) Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within membrane lipid metabolic process and regulation of gene expression. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP2	NM_199321.3	c.626-177C>G		intron_variant		ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3	c.560-177C>G		intron_variant			NP_942141.2
ZPBP2	XM_047435318.1	c.626-177C>G		intron_variant			XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9	c.626-177C>G		intron_variant		1	NM_199321.3	ENSP00000335384	P1
ZPBP2	ENST00000377940.3	c.560-177C>G		intron_variant		1		ENSP00000367174
ZPBP2	ENST00000583811.5	c.272-177C>G		intron_variant		3		ENSP00000462463
ZPBP2	ENST00000584588.5	c.407-177C>G		intron_variant		5		ENSP00000462067

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75631 AN: 151912 Hom.: 19042 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.498 AC: 75744 AN: 152030 Hom.: 19088 Cov.: 32 AF XY: 0.497 AC XY: 36949 AN XY: 74290

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.476

Alfa AF: 0.479 Hom.: 2080

Bravo AF: 0.484

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.86

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: rs12936231; hg19: chr17-38029120;