7-49983526-C-T

Variant names:

• chr7-49983526-C-T
• rs988392
• NM_007009.3:c.784-7G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_007009.3(ZPBP):​c.784-7G>A variant causes a splice region, 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.80 (48493 hom., cov: 31)
  • Exomes 𝑓: 0.80 (445987 hom.)
• Consequence: ZPBP NM_007009.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002088
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.637
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 66

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 3059140.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007009.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP	NM_007009.3	MANE Select	c.784-7G>A		splice_region intron	N/A	NP_008940.2	Q9BS86-1
	ZPBP	NM_001159878.2		c.781-7G>A		splice_region intron	N/A	NP_001153350.1	Q9BS86-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP	ENST00000046087.7	TSL:1 MANE Select	c.784-7G>A		splice_region intron	N/A	ENSP00000046087.2	Q9BS86-1
	ZPBP	ENST00000419417.5	TSL:1	c.781-7G>A		splice_region intron	N/A	ENSP00000402071.1	Q9BS86-2
	ZPBP	ENST00000903720.1		c.412-7G>A		splice_region intron	N/A	ENSP00000573779.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121120 AN: 151830 Hom.: 48459 Cov.: 31

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

GnomAD2 exomes AF: 0.774 AC: 176742 AN: 228350 AF XY: 0.775

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 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.: 22 AF XY: 0.795 AC XY: 554837 AN XY: 697974

African (AFR) AF: 0.811 AC: 25838 AN: 31840

American (AMR) AF: 0.634 AC: 26795 AN: 42234

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 18816 AN: 25500

East Asian (EAS) AF: 0.886 AC: 34641 AN: 39088

South Asian (SAS) AF: 0.740 AC: 60999 AN: 82418

European-Finnish (FIN) AF: 0.833 AC: 42856 AN: 51434

Middle Eastern (MID) AF: 0.720 AC: 3680 AN: 5114

European-Non Finnish (NFE) AF: 0.805 AC: 855971 AN: 1063708

Other (OTH) AF: 0.788 AC: 45757 AN: 58078

GnomAD4 genome AF: 0.798 AC: 121210 AN: 151948 Hom.: 48493 Cov.: 31 AF XY: 0.797 AC XY: 59188 AN XY: 74248

African (AFR) AF: 0.817 AC: 33856 AN: 41464

American (AMR) AF: 0.693 AC: 10569 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2530 AN: 3466

East Asian (EAS) AF: 0.886 AC: 4593 AN: 5182

South Asian (SAS) AF: 0.730 AC: 3515 AN: 4814

European-Finnish (FIN) AF: 0.838 AC: 8836 AN: 10546

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54699 AN: 67912

Other (OTH) AF: 0.768 AC: 1621 AN: 2110

Alfa AF: 0.792 Hom.: 15827

Bravo AF: 0.786

Asia WGS AF: 0.751 AC: 2603 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZPBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs988392; hg19: chr7-50023122;