rs6963083

Variant names:

• chr7-49869855-G-A
• rs6963083
• NM_198570.5:c.827-42179G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-49869855-G-A
• chr7-49869855-G-C

Variant summary

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

The NM_198570.5(VWC2):​c.827-42179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,772 control chromosomes in the GnomAD database, including 35,204 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 0.67 (35204 hom., cov: 31)
• Consequence: VWC2 NM_198570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 2 publications found

Genes affected

VWC2 (HGNC:30200): (von Willebrand factor C domain containing 2) This gene encodes a secreted bone morphogenic protein antagonist. The encoded protein is possibly involved in neural function and development and may have a role in cell adhesion.[provided by RefSeq, Oct 2009]

ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

ZPBP Gene-Disease associations (from GenCC):

• spermatogenic failure 66

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198570.5. 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
	VWC2	NM_198570.5	MANE Select	c.827-42179G>A		intron	N/A	NP_940972.2
	VWC2	NR_136188.1		n.930-42179G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWC2	ENST00000340652.5	TSL:1 MANE Select	c.827-42179G>A		intron	N/A	ENSP00000341819.3
	ZPBP	ENST00000465922.1	TSL:4	n.510-19341C>T		intron	N/A
	ZPBP	ENST00000491129.5	TSL:3	n.517-19341C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102052 AN: 151654 Hom.: 35193 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.673 AC: 102105 AN: 151772 Hom.: 35204 Cov.: 31 AF XY: 0.675 AC XY: 50058 AN XY: 74144

African (AFR) AF: 0.529 AC: 21858 AN: 41336

American (AMR) AF: 0.610 AC: 9284 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2315 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4558 AN: 5164

South Asian (SAS) AF: 0.568 AC: 2727 AN: 4798

European-Finnish (FIN) AF: 0.802 AC: 8431 AN: 10512

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50584 AN: 67952

Other (OTH) AF: 0.655 AC: 1384 AN: 2112

Alfa AF: 0.709 Hom.: 123177

Bravo AF: 0.654

Asia WGS AF: 0.660 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.40
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6963083; hg19: chr7-49909451;