dbSNP rs2075671: ZAN:c.932-67G>A (chr7-100747483-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2544 hom., cov: 31)

Exomes 𝑓: 0.21 ( 27535 hom. )

Consequence

ZAN
NM_003386.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.595

Publications

41 publications found

Variant links:

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]

ZAN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003386.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZAN	NM_003386.3	MANE Select	c.932-67G>A	intron	N/A	NP_003377.2	Q9Y493-1
ZAN	NM_173059.3		c.932-67G>A	intron	N/A	NP_775082.2	Q9Y493-6
ZAN	NR_111917.2		n.1128-67G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZAN	ENST00000613979.5	TSL:1 MANE Select	c.932-67G>A	intron	N/A	ENSP00000480750.1	Q9Y493-1
ZAN	ENST00000620596.4	TSL:1	c.932-67G>A	intron	N/A	ENSP00000481742.1	Q9Y493-6
ZAN	ENST00000538115.5	TSL:1	n.932-67G>A	intron	N/A	ENSP00000445091.2	Q9Y493-4

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24932

AN:

152048

Hom.:

2540

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9576

19152

28729

38305

47881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5784

11568

17352

23136

28920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.164

AC:

24936

AN:

152166

Hom.:

2544

Cov.:

AF XY:

0.163

AC XY:

12102

AN XY:

74374

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15449

AN:

67988

Other (OTH)

AF:

0.140

AC:

296

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1036

2072

3108

4144

5180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.24

(source)

DANN

Benign

0.54

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over