Variant 7-49983526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007009.3(ZPBP):c.784-7G>A 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 0.797 in 1,551,362 control chromosomes in the GnomAD database, including 494,480 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 (★).

Frequency

Genomes: 𝑓 0.80 ( 48493 hom., cov: 31)

Exomes 𝑓: 0.80 ( 445987 hom. )

Consequence

ZPBP
NM_007009.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002088

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.637

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-49983526-C-T is Benign according to our data. Variant chr7-49983526-C-T is described in ClinVar as [Benign]. Clinvar id is 3059140.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.784-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000046087.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ZPBP	ENST00000046087.7 linkuse as main transcript	c.784-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_007009.3	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.781-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		A2	Q9BS86-2
ZPBP	ENST00000491129.5 linkuse as main transcript	n.241-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121120

AN:

151830

Hom.:

48459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.887

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.838

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.770

GnomAD3 exomes

AF:

0.774

AC:

176742

AN:

228350

Hom.:

68940

AF XY:

0.775

AC XY:

95829

AN XY:

123702

show subpopulations

Gnomad AFR exome

AF:

0.811

Gnomad AMR exome

AF:

0.627

Gnomad ASJ exome

AF:

0.741

Gnomad EAS exome

AF:

0.889

Gnomad SAS exome

AF:

0.738

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.798

Gnomad OTH exome

AF:

0.773

GnomAD4 exome

AF:

0.797

AC:

1115353

AN:

1399414

Hom.:

445987

Cov.:

AF XY:

0.795

AC XY:

554837

AN XY:

697974

show subpopulations

Gnomad4 AFR exome

AF:

0.811

Gnomad4 AMR exome

AF:

0.634

Gnomad4 ASJ exome

AF:

0.738

Gnomad4 EAS exome

AF:

0.886

Gnomad4 SAS exome

AF:

0.740

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.805

Gnomad4 OTH exome

AF:

0.788

GnomAD4 genome

AF:

0.798

AC:

121210

AN:

151948

Hom.:

48493

Cov.:

AF XY:

0.797

AC XY:

59188

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.817

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.730

Gnomad4 EAS

AF:

0.886

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.838

Gnomad4 NFE

AF:

0.805

Gnomad4 OTH

AF:

0.768

Alfa

AF:

0.792

Hom.:

15562

Bravo

AF:

0.786

Asia WGS

AF:

0.751

AC:

2603

AN:

3468

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 submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.90

CADD

Benign

1.2

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

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