Variant 7-50018323-A-G details in Genebe, Genetics Data Aggregator

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

Splicing: ADA: 0.001836

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]

ZPBP links:

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	Protein	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.707-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000046087.7	NP_008940.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ZPBP	ENST00000046087.7 linkuse as main transcript	c.707-7T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_007009.3	ENSP00000046087	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.704-7T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000402071	A2	Q9BS86-2
ZPBP	ENST00000491129.5 linkuse as main transcript	n.241-34804T>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00486

AC:

738

AN:

151984

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00524

Asia WGS

AF:

0.000869

AC:

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 provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 12, 2019

This 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over