rs2075671

Variant names:

• chr7-100747483-G-A
• rs2075671
• NM_003386.3:c.932-67G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZAN	NM_003386.3	c.932-67G>A		intron_variant	Intron 8 of 47	ENST00000613979.5	NP_003377.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5	c.932-67G>A		intron_variant	Intron 8 of 47	1	NM_003386.3	ENSP00000480750.1

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

African (AFR) AF: 0.0330 AC: 920 AN: 27878

American (AMR) AF: 0.172 AC: 7598 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4428 AN: 24322

East Asian (EAS) AF: 0.139 AC: 5314 AN: 38350

South Asian (SAS) AF: 0.136 AC: 10996 AN: 80576

European-Finnish (FIN) AF: 0.256 AC: 13631 AN: 53150

Middle Eastern (MID) AF: 0.109 AC: 568 AN: 5204

European-Non Finnish (NFE) AF: 0.226 AC: 193865 AN: 857604

Other (OTH) AF: 0.192 AC: 9810 AN: 51108

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

African (AFR) AF: 0.0414 AC: 1720 AN: 41524

American (AMR) AF: 0.158 AC: 2406 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.145 AC: 752 AN: 5182

South Asian (SAS) AF: 0.133 AC: 639 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2784 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15449 AN: 67988

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.201 Hom.: 10671

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
PhyloP100		-0.59
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

Other links and lift over

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