rs5015755

Variant names:

• chr7-100415779-G-T
• rs5015755
• NM_001386010.1:c.754+196C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386010.1(ZCWPW1):​c.754+196C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,114 control chromosomes in the GnomAD database, including 1,673 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 0.15 (1673 hom., cov: 30)
• Consequence: ZCWPW1 NM_001386010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 12 publications found

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]

ENSG00000289690 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	NM_001386010.1	MANE Select	c.754+196C>A		intron	N/A	NP_001372939.1
	ZCWPW1	NM_017984.6		c.751+196C>A		intron	N/A	NP_060454.3
	ZCWPW1	NM_001386016.1		c.754+196C>A		intron	N/A	NP_001372945.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	ENST00000684423.1	MANE Select	c.754+196C>A		intron	N/A	ENSP00000507762.1
	ZCWPW1	ENST00000398027.6	TSL:1	c.751+196C>A		intron	N/A	ENSP00000381109.2
	ZCWPW1	ENST00000490721.5	TSL:1	c.391+196C>A		intron	N/A	ENSP00000419187.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22246 AN: 151996 Hom.: 1675 Cov.: 30

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22246 AN: 152114 Hom.: 1673 Cov.: 30 AF XY: 0.146 AC XY: 10835 AN XY: 74342

African (AFR) AF: 0.122 AC: 5070 AN: 41486

American (AMR) AF: 0.112 AC: 1720 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3468

East Asian (EAS) AF: 0.161 AC: 833 AN: 5184

South Asian (SAS) AF: 0.124 AC: 601 AN: 4828

European-Finnish (FIN) AF: 0.187 AC: 1973 AN: 10552

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11186 AN: 67978

Other (OTH) AF: 0.132 AC: 279 AN: 2110

Alfa AF: 0.158 Hom.: 8609

Bravo AF: 0.140

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5015755; hg19: chr7-100013402;