dbSNP rs5015756: ZCWPW1:c.754+141A>G (chr7-100415834-T-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_001386010.1(ZCWPW1):c.754+141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,144,758 control chromosomes in the GnomAD database, including 172,640 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 0.56 ( 24595 hom., cov: 32)

Exomes 𝑓: 0.54 ( 148045 hom. )

Consequence

ZCWPW1
NM_001386010.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.219

Publications

22 publications found

Variant links:

Genes affected

ZCWPW1 (HGNC:23486): (zinc finger CW-type and PWWP domain containing 1) Enables methyl-CpG binding activity and methylated histone binding activity. Predicted to be involved in meiosis I; positive regulation of DNA metabolic process; and spermatogenesis. Predicted to act upstream of or within homologous chromosome pairing at meiosis. Predicted to be located in XY body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZCWPW1 links:

ENSG00000289690 (HGNC:):

ENSG00000289690 links:

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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=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZCWPW1	NM_001386010.1	MANE Select	c.754+141A>G	intron	N/A	NP_001372939.1
ZCWPW1	NM_017984.6		c.751+141A>G	intron	N/A	NP_060454.3
ZCWPW1	NM_001386016.1		c.754+141A>G	intron	N/A	NP_001372945.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZCWPW1	ENST00000684423.1	MANE Select	c.754+141A>G	intron	N/A	ENSP00000507762.1
ZCWPW1	ENST00000398027.6	TSL:1	c.751+141A>G	intron	N/A	ENSP00000381109.2
ZCWPW1	ENST00000490721.5	TSL:1	c.391+141A>G	intron	N/A	ENSP00000419187.1

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85195

AN:

151936

Hom.:

24570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.563

GnomAD4 exome

AF:

0.540

AC:

535858

AN:

992704

Hom.:

148045

AF XY:

0.544

AC XY:

271887

AN XY:

499846

show subpopulations

African (AFR)

AF:

0.669

AC:

15570

AN:

23264

American (AMR)

AF:

0.325

AC:

9333

AN:

28746

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

9981

AN:

17764

East Asian (EAS)

AF:

0.322

AC:

11878

AN:

36914

South Asian (SAS)

AF:

0.581

AC:

34827

AN:

59984

European-Finnish (FIN)

AF:

0.564

AC:

20614

AN:

36580

Middle Eastern (MID)

AF:

0.626

AC:

2906

AN:

4642

European-Non Finnish (NFE)

AF:

0.550

AC:

407086

AN:

740668

Other (OTH)

AF:

0.536

AC:

23663

AN:

44142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11474

22948

34421

45895

57369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10158

20316

30474

40632

50790

<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:

0.561

AC:

85265

AN:

152054

Hom.:

24595

Cov.:

AF XY:

0.557

AC XY:

41365

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.658

AC:

27282

AN:

41464

American (AMR)

AF:

0.433

AC:

6613

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1944

AN:

3468

East Asian (EAS)

AF:

0.278

AC:

1441

AN:

5184

South Asian (SAS)

AF:

0.565

AC:

2724

AN:

4824

European-Finnish (FIN)

AF:

0.552

AC:

5833

AN:

10558

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37521

AN:

67956

Other (OTH)

AF:

0.563

AC:

1187

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1868

3736

5605

7473

9341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.558

Hom.:

74743

Bravo

AF:

0.554

Asia WGS

AF:

0.436

AC:

1519

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.3

(source)

DANN

Benign

0.62

PhyloP100

0.22

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over