rs1339647

chr1-237881511-C-Gchr1-237881511-C-T

Variant summary

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

The NR_027247.2(LOC100130331):n.308-955C>G variant causes a intron, non coding transcript 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: LOC100130331 NR_027247.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

Genes affected

(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=-0.81).
• 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/exons	MANE	UniProt
LOC100130331	NR_027247.2	n.308-955C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000450451.1	n.308-955C>G		intron_variant, non_coding_transcript_variant		1
ZP4	ENST00000611898.4	c.*45+866G>C		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0114

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0748

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

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: rs1339647; hg19: chr1-238044811;