7-50018323-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_007009.3(ZPBP):​c.707-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,586,124 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 10 hom. )

Consequence

ZPBP
NM_007009.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.001836
2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.34
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 -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 7-50018323-A-G is Benign according to our data. Variant chr7-50018323-A-G is described in ClinVar as [Benign]. Clinvar id is 3043780.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00487 (741/152102) while in subpopulation AFR AF= 0.0167 (695/41556). AF 95% confidence interval is 0.0157. There are 4 homozygotes in gnomad4. There are 350 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZPBPNM_007009.3 linkuse as main transcriptc.707-7T>C splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000046087.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZPBPENST00000046087.7 linkuse as main transcriptc.707-7T>C splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_007009.3 P4Q9BS86-1
ZPBPENST00000419417.5 linkuse as main transcriptc.704-7T>C splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 A2Q9BS86-2
ZPBPENST00000491129.5 linkuse as main transcriptn.241-34804T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00486
AC:
738
AN:
151984
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0167
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00135
AC:
335
AN:
248572
Hom.:
1
AF XY:
0.00111
AC XY:
149
AN XY:
134588
show subpopulations
Gnomad AFR exome
AF:
0.0177
Gnomad AMR exome
AF:
0.000933
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000125
Gnomad OTH exome
AF:
0.000827
GnomAD4 exome
AF:
0.000538
AC:
771
AN:
1434022
Hom.:
10
Cov.:
26
AF XY:
0.000502
AC XY:
359
AN XY:
715204
show subpopulations
Gnomad4 AFR exome
AF:
0.0180
Gnomad4 AMR exome
AF:
0.00103
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000351
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000422
Gnomad4 OTH exome
AF:
0.00121
GnomAD4 genome
AF:
0.00487
AC:
741
AN:
152102
Hom.:
4
Cov.:
32
AF XY:
0.00471
AC XY:
350
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0167
Gnomad4 AMR
AF:
0.00197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00158
Hom.:
3
Bravo
AF:
0.00524
Asia WGS
AF:
0.000869
AC:
3
AN:
3466
EpiCase
AF:
0.0000547
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ZPBP-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 12, 2019This 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
-0.31
CADD
Benign
15
DANN
Benign
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0018
dbscSNV1_RF
Benign
0.068
SpliceAI score (max)
0.10
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: rs139249676; hg19: chr7-50057919; API