Variant 7-50089625-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_007009.3(ZPBP):c.208+4T>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZPBP
NM_007009.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002803

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.388

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-50089625-A-C is Benign according to our data. Variant chr7-50089625-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044614.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.208+4T>G		splice_donor_region_variant, intron_variant		ENST00000046087.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ZPBP	ENST00000046087.7 linkuse as main transcript	c.208+4T>G	splice_donor_region_variant, intron_variant	1	NM_007009.3	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.208+4T>G	splice_donor_region_variant, intron_variant	1		A2	Q9BS86-2
ZPBP	ENST00000450231.1 linkuse as main transcript	c.91+4T>G	splice_donor_region_variant, intron_variant	3
ZPBP	ENST00000413331.1 linkuse as main transcript	c.*185+4T>G	splice_donor_region_variant, intron_variant, NMD_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152034

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000598

AC:

858

AN:

1434858

Hom.:

Cov.:

AF XY:

0.000532

AC XY:

380

AN XY:

714772

show subpopulations

Gnomad4 AFR exome

AF:

0.000487

Gnomad4 AMR exome

AF:

0.0000903

Gnomad4 ASJ exome

AF:

0.000117

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.000271

Gnomad4 FIN exome

AF:

0.0000942

Gnomad4 NFE exome

AF:

0.000711

Gnomad4 OTH exome

AF:

0.000405

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000197

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZPBP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2020

This variant is classified as likely 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

-0.57

CADD

Benign

2.3

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.044

SpliceAI score (max)

0.050

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