dbSNP rs1054609: ZPBP2:c.*215A>C (chr17-39877024-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199321.3(ZPBP2):c.*215A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 444,314 control chromosomes in the GnomAD database, including 40,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12605 hom., cov: 31)

Exomes 𝑓: 0.43 ( 28093 hom. )

Consequence

ZPBP2
NM_199321.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

23 publications found

Variant links:

Genes affected

ZPBP2 (HGNC:20678): (zona pellucida binding protein 2) Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within membrane lipid metabolic process and regulation of gene expression. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZPBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPBP2	NM_199321.3 link	c.*215A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000348931.9	NP_955353.1	Q6X784-1
ZPBP2	NM_198844.3 link	c.*215A>C		3_prime_UTR_variant	Exon 7 of 7		NP_942141.2	Q6X784-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZPBP2	ENST00000348931.9 link	c.*215A>C	3_prime_UTR_variant	Exon 8 of 8	1	NM_199321.3	ENSP00000335384.5	Q6X784-1
ZPBP2	ENST00000377940.3 link	c.*215A>C	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000367174.3	Q6X784-2
ZPBP2	ENST00000584588.5 link	c.*215A>C	3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000462067.1	J3KRM0
ZPBP2	ENST00000583811.5 link	c.*222A>C	downstream_gene_variant		3		ENSP00000462463.1	J3KSF6

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60410

AN:

151872

Hom.:

12589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.387

GnomAD4 exome

AF:

0.433

AC:

126517

AN:

292324

Hom.:

28093

Cov.:

AF XY:

0.428

AC XY:

66194

AN XY:

154480

show subpopulations

African (AFR)

AF:

0.301

AC:

2654

AN:

8820

American (AMR)

AF:

0.357

AC:

4713

AN:

13190

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

3464

AN:

8122

East Asian (EAS)

AF:

0.268

AC:

4845

AN:

18096

South Asian (SAS)

AF:

0.365

AC:

11435

AN:

31318

European-Finnish (FIN)

AF:

0.519

AC:

7975

AN:

15356

Middle Eastern (MID)

AF:

0.421

AC:

506

AN:

1202

European-Non Finnish (NFE)

AF:

0.466

AC:

83912

AN:

179894

Other (OTH)

AF:

0.430

AC:

7013

AN:

16326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3368

6736

10103

13471

16839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

746

1492

2238

2984

3730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.398

AC:

60464

AN:

151990

Hom.:

12605

Cov.:

AF XY:

0.400

AC XY:

29706

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.290

AC:

12009

AN:

41452

American (AMR)

AF:

0.393

AC:

5994

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1440

AN:

3466

East Asian (EAS)

AF:

0.270

AC:

1398

AN:

5184

South Asian (SAS)

AF:

0.372

AC:

1789

AN:

4806

European-Finnish (FIN)

AF:

0.532

AC:

5604

AN:

10542

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.452

AC:

30708

AN:

67964

Other (OTH)

AF:

0.387

AC:

816

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1811

3622

5434

7245

9056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.401

Hom.:

5496

Bravo

AF:

0.376

Asia WGS

AF:

0.386

AC:

1339

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over