Genetic Variant ZPBP2:c.889+27C>T (chr17-39875461-C-T) – 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.889+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,505,442 control chromosomes in the GnomAD database, including 148,955 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 ( 12599 hom., cov: 32)

Exomes 𝑓: 0.44 ( 136356 hom. )

Consequence

ZPBP2
NM_199321.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

Publications

47 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=-0.79).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199321.3. 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
	ZPBP2	NM_199321.3	MANE Select	c.889+27C>T		intron	N/A	NP_955353.1	Q6X784-1
	ZPBP2	NM_198844.3		c.823+27C>T		intron	N/A	NP_942141.2	Q6X784-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZPBP2	ENST00000348931.9	TSL:1 MANE Select	c.889+27C>T	intron	N/A	ENSP00000335384.5	Q6X784-1
ZPBP2	ENST00000377940.3	TSL:1	c.823+27C>T	intron	N/A	ENSP00000367174.3	Q6X784-2
ZPBP2	ENST00000584588.5	TSL:5	c.670+27C>T	intron	N/A	ENSP00000462067.1	J3KRM0

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60385

AN:

151782

Hom.:

12583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.387

GnomAD2 exomes

AF:

0.387

AC:

71195

AN:

184078

AF XY:

0.391

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.445

AC:

601710

AN:

1353542

Hom.:

136356

Cov.:

AF XY:

0.442

AC XY:

296359

AN XY:

670300

show subpopulations

African (AFR)

AF:

0.277

AC:

8210

AN:

29588

American (AMR)

AF:

0.323

AC:

10582

AN:

32770

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

9767

AN:

23296

East Asian (EAS)

AF:

0.255

AC:

9474

AN:

37140

South Asian (SAS)

AF:

0.356

AC:

24694

AN:

69346

European-Finnish (FIN)

AF:

0.512

AC:

25285

AN:

49364

Middle Eastern (MID)

AF:

0.390

AC:

2111

AN:

5410

European-Non Finnish (NFE)

AF:

0.465

AC:

488265

AN:

1050848

Other (OTH)

AF:

0.418

AC:

23322

AN:

55780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

13496

26993

40489

53986

67482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14704

29408

44112

58816

73520

<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:

60439

AN:

151900

Hom.:

12599

Cov.:

AF XY:

0.400

AC XY:

29696

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.290

AC:

11999

AN:

41410

American (AMR)

AF:

0.393

AC:

6000

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

1444

AN:

3466

East Asian (EAS)

AF:

0.270

AC:

1398

AN:

5180

South Asian (SAS)

AF:

0.372

AC:

1789

AN:

4814

European-Finnish (FIN)

AF:

0.532

AC:

5592

AN:

10502

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.452

AC:

30696

AN:

67942

Other (OTH)

AF:

0.386

AC:

816

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1809

3619

5428

7238

9047

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:

0.428

Hom.:

32252

Bravo

AF:

0.376

Asia WGS

AF:

0.385

AC:

1336

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.9

(source)

DANN

Benign

0.79

PhyloP100

1.8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over