Variant 7-50058101-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

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 (no stars).

Frequency

Genomes: 𝑓 0.031 ( 89 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1125 hom. )

Consequence

ZPBP
NM_007009.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided 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]

ZPBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

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 no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.268 with no splicing effect.

BS1

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

High Homozygotes in GnomAd4 at 89 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.375T>C	p.Leu125=	synonymous_variant	4/8	ENST00000046087.7	NP_008940.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP	ENST00000046087.7 linkuse as main transcript	c.375T>C	p.Leu125=	synonymous_variant	4/8	1	NM_007009.3	ENSP00000046087	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.372T>C	p.Leu124=	synonymous_variant	4/8	1		ENSP00000402071	A2	Q9BS86-2

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4726

AN:

152198

Hom.:

Cov.:

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.:

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

AF:

0.0310

AC:

4727

AN:

152316

Hom.:

Cov.:

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:

AN:

3478

EpiCase

AF:

0.0467

EpiControl

AF:

0.0493

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

Feb 18, 2020

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

-0.64

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.

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