rs1000215

chr7-100406920-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386010.1(ZCWPW1):c.1069-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 831,632 control chromosomes in the GnomAD database, including 15,781 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 0.21 (3714 hom., cov: 32)
  • Exomes 𝑓: 0.18 (12067 hom.)
• Consequence: ZCWPW1 NM_001386010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCWPW1	NM_001386010.1	c.1069-122A>G		intron_variant		ENST00000684423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCWPW1	ENST00000684423.1	c.1069-122A>G		intron_variant			NM_001386010.1	P4
	ENST00000695704.1	n.505+3086T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32229 AN: 152038 Hom.: 3690 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.179 AC: 121693 AN: 679476 Hom.: 12067 AF XY: 0.178 AC XY: 62487 AN XY: 350186

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.0342

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.212 AC: 32291 AN: 152156 Hom.: 3714 Cov.: 32 AF XY: 0.210 AC XY: 15637 AN XY: 74394

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0336

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.212

Alfa AF: 0.196 Hom.: 3004

Bravo AF: 0.210

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.5
Dann	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs1000215; hg19: chr7-100004543;