rs5015756

Positions:

• chr7-100415834-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCWPW1	NM_001386010.1	c.754+141A>G		intron_variant		ENST00000684423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCWPW1	ENST00000684423.1	c.754+141A>G		intron_variant			NM_001386010.1	P4
	ENST00000695704.1	n.506-1499T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85195 AN: 151936 Hom.: 24570 Cov.: 32

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

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.564

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.561 AC: 85265 AN: 152054 Hom.: 24595 Cov.: 32 AF XY: 0.557 AC XY: 41365 AN XY: 74310

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.563

Alfa AF: 0.555 Hom.: 47705

Bravo AF: 0.554

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.3
DANN	Benign	0.62

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: rs5015756; hg19: chr7-100013457;