1-237881117-C-T

Position:

• chr1-237881117-C-T

Variant summary

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

The ENST00000611898.4(ZP4):​c.*45+1260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,134 control chromosomes in the GnomAD database, including 1,478 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 0.14 (1478 hom., cov: 32)
• Consequence: ZP4 ENST00000611898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

Genes affected

ENSG00000237250 (HGNC:):

ZP4 (HGNC:15770): (zona pellucida glycoprotein 4) The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a consensus furin cleavage site, and a C-terminal transmembrane domain. It is hypothesized that furin cleavage results in release of the mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the requirement for furin cleavage in this process remains controversial based on mouse studies. Previously, this gene has been referred to as ZP1 or ZPB and thought to have similar functions as mouse Zp1. However, a human gene with higher similarity and chromosomal synteny to mouse Zp1 has been assigned the symbol ZP1 and this gene has been assigned the symbol ZP4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100130331	NR_027247.2	n.308-1349C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000237250	ENST00000450451.1	n.308-1349C>T		intron_variant		1
ZP4	ENST00000611898.4	c.*45+1260G>A		intron_variant		5		ENSP00000482304.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20945 AN: 152016 Hom.: 1474 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0921

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.138 AC: 20968 AN: 152134 Hom.: 1478 Cov.: 32 AF XY: 0.137 AC XY: 10202 AN XY: 74374

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0921

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.143

Alfa AF: 0.134 Hom.: 263

Bravo AF: 0.145

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.30

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: rs1361358; hg19: chr1-238044417;