rs2075671

Positions:

• chr7-100747483-G-A
• chr7-100747483-G-C

Variant summary

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

The NM_003386.3(ZAN):​c.932-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,334,498 control chromosomes in the GnomAD database, including 30,079 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 0.16 (2544 hom., cov: 31)
  • Exomes 𝑓: 0.21 (27535 hom.)
• Consequence: ZAN NM_003386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

Genes affected

ZAN (HGNC:12857): (zonadhesin) This gene encodes a protein that functions in the species specificity of sperm adhesion to the egg zona pellucida. The encoded protein is located in the acrosome and may be involved in signaling or gamete recognition. An allelic polymorphism in this gene results in both functional and frameshifted alleles; the reference genome represents the functional allele. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -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 = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAN	NM_003386.3	c.932-67G>A		intron_variant		ENST00000613979.5	NP_003377.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5	c.932-67G>A		intron_variant		1	NM_003386.3	ENSP00000480750	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24932 AN: 152048 Hom.: 2540 Cov.: 31

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.209 AC: 247130 AN: 1182332 Hom.: 27535 AF XY: 0.207 AC XY: 124771 AN XY: 602090

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.164 AC: 24936 AN: 152166 Hom.: 2544 Cov.: 31 AF XY: 0.163 AC XY: 12102 AN XY: 74374

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.140

Alfa AF: 0.201 Hom.: 3912

Bravo AF: 0.153

Asia WGS AF: 0.135 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.54

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: rs2075671; hg19: chr7-100345106; COSMIC: COSV61808360;