rs1339647

Variant names:

• chr1-237881511-C-G
• rs1339647
• ENST00000450451.1:n.308-955C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-237881511-C-G
• chr1-237881511-C-T

Variant summary

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

The ENST00000450451.1(ENSG00000237250):​n.308-955C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,164 control chromosomes in the GnomAD database, including 1,899 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 0.10 (1899 hom., cov: 32)
• Consequence: ENSG00000237250 ENST00000450451.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 1 publications found

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]

ZP4 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100130331	NR_027247.2	n.308-955C>G		intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237250	ENST00000450451.1	n.308-955C>G		intron_variant	Intron 3 of 11	1
ZP4	ENST00000611898.4	c.*45+866G>C		intron_variant	Intron 12 of 12	5		ENSP00000482304.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15404 AN: 152046 Hom.: 1897 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.101 AC: 15431 AN: 152164 Hom.: 1899 Cov.: 32 AF XY: 0.102 AC XY: 7597 AN XY: 74388

African (AFR) AF: 0.290 AC: 12022 AN: 41468

American (AMR) AF: 0.101 AC: 1544 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5186

South Asian (SAS) AF: 0.124 AC: 599 AN: 4830

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10600

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 827 AN: 68016

Other (OTH) AF: 0.0748 AC: 158 AN: 2112

Alfa AF: 0.0145 Hom.: 21

Bravo AF: 0.112

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.58
PhyloP100		0.23

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

Other links and lift over

dbSNP: rs1339647; hg19: chr1-238044811;