rs1000215

Variant names:

• chr7-100406920-T-C
• rs1000215
• NM_001386010.1:c.1069-122A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	NM_001386010.1	MANE Select	c.1069-122A>G		intron	N/A	NP_001372939.1	A0A804HK41
	ZCWPW1	NM_017984.6		c.1066-122A>G		intron	N/A	NP_060454.3
	ZCWPW1	NM_001386016.1		c.1069-122A>G		intron	N/A	NP_001372945.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCWPW1	ENST00000684423.1	MANE Select	c.1069-122A>G		intron	N/A	ENSP00000507762.1	A0A804HK41
	ZCWPW1	ENST00000398027.6	TSL:1	c.1066-122A>G		intron	N/A	ENSP00000381109.2	Q9H0M4-1
	ZCWPW1	ENST00000490721.5	TSL:1	c.706-122A>G		intron	N/A	ENSP00000419187.1	Q9H0M4-4

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

African (AFR) AF: 0.278 AC: 4652 AN: 16758

American (AMR) AF: 0.113 AC: 2742 AN: 24294

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 3493 AN: 16234

East Asian (EAS) AF: 0.0342 AC: 1116 AN: 32628

South Asian (SAS) AF: 0.125 AC: 6755 AN: 53932

European-Finnish (FIN) AF: 0.230 AC: 8543 AN: 37084

Middle Eastern (MID) AF: 0.210 AC: 590 AN: 2804

European-Non Finnish (NFE) AF: 0.190 AC: 87545 AN: 461852

Other (OTH) AF: 0.185 AC: 6257 AN: 33890

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

African (AFR) AF: 0.287 AC: 11926 AN: 41494

American (AMR) AF: 0.145 AC: 2214 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3468

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5184

South Asian (SAS) AF: 0.122 AC: 587 AN: 4826

European-Finnish (FIN) AF: 0.234 AC: 2482 AN: 10592

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13340 AN: 67988

Other (OTH) AF: 0.212 AC: 448 AN: 2110

Alfa AF: 0.198 Hom.: 4054

Bravo AF: 0.210

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.35
PhyloP100		0.56
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1000215;

hg19: chr7-100004543;