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GeneBe

7-50058101-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_007009.3(ZPBP):c.375T>C(p.Leu125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,794 control chromosomes in the GnomAD database, including 1,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.031 ( 89 hom., cov: 32)
Exomes 𝑓: 0.037 ( 1125 hom. )

Consequence

ZPBP
NM_007009.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.268
Variant links:
Genes affected
ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-50058101-A-G is Benign according to our data. Variant chr7-50058101-A-G is described in ClinVar as [Benign]. Clinvar id is 3037675.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.268 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.031 (4727/152316) while in subpopulation NFE AF= 0.045 (3060/68028). AF 95% confidence interval is 0.0437. There are 89 homozygotes in gnomad4. There are 2212 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 89 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZPBPNM_007009.3 linkuse as main transcriptc.375T>C p.Leu125= synonymous_variant 4/8 ENST00000046087.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZPBPENST00000046087.7 linkuse as main transcriptc.375T>C p.Leu125= synonymous_variant 4/81 NM_007009.3 P4Q9BS86-1
ZPBPENST00000419417.5 linkuse as main transcriptc.372T>C p.Leu124= synonymous_variant 4/81 A2Q9BS86-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0311
AC:
4726
AN:
152198
Hom.:
89
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0114
Gnomad AMI
AF:
0.0910
Gnomad AMR
AF:
0.0235
Gnomad ASJ
AF:
0.0473
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.0124
Gnomad FIN
AF:
0.0409
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0450
Gnomad OTH
AF:
0.0335
GnomAD3 exomes
AF:
0.0311
AC:
7817
AN:
251210
Hom.:
163
AF XY:
0.0315
AC XY:
4278
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.0102
Gnomad AMR exome
AF:
0.0190
Gnomad ASJ exome
AF:
0.0472
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0127
Gnomad FIN exome
AF:
0.0417
Gnomad NFE exome
AF:
0.0441
Gnomad OTH exome
AF:
0.0352
GnomAD4 exome
AF:
0.0370
AC:
54116
AN:
1461478
Hom.:
1125
Cov.:
32
AF XY:
0.0368
AC XY:
26741
AN XY:
727044
show subpopulations
Gnomad4 AFR exome
AF:
0.0100
Gnomad4 AMR exome
AF:
0.0195
Gnomad4 ASJ exome
AF:
0.0465
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0123
Gnomad4 FIN exome
AF:
0.0412
Gnomad4 NFE exome
AF:
0.0415
Gnomad4 OTH exome
AF:
0.0341
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0310
AC:
4727
AN:
152316
Hom.:
89
Cov.:
32
AF XY:
0.0297
AC XY:
2212
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0115
Gnomad4 AMR
AF:
0.0235
Gnomad4 ASJ
AF:
0.0473
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.0124
Gnomad4 FIN
AF:
0.0409
Gnomad4 NFE
AF:
0.0450
Gnomad4 OTH
AF:
0.0331
Alfa
AF:
0.0417
Hom.:
241
Bravo
AF:
0.0295
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.0467
EpiControl
AF:
0.0493

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ZPBP-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 18, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
6.6
Dann
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76027725; hg19: chr7-50097697; API