rs1893316

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_053054.4(CATSPER1):c.54C>T(p.Asn18Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,613,956 control chromosomes in the GnomAD database, including 50,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3921 hom., cov: 32)

Exomes 𝑓: 0.24 ( 46131 hom. )

Consequence

CATSPER1
NM_053054.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.110

Publications

27 publications found

Variant links:

Genes affected

CATSPER1 (HGNC:17116): (cation channel sperm associated 1) Calcium ions play a primary role in the regulation of sperm motility. This gene belongs to a family of putative cation channels that are specific to spermatozoa and localize to the flagellum. The protein family features a single repeat with six membrane-spanning segments and a predicted calcium-selective pore region. [provided by RefSeq, Jul 2008]

CATSPER1 Gene-Disease associations (from GenCC):

non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 7
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CATSPER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-66026326-G-A is Benign according to our data. Variant chr11-66026326-G-A is described in ClinVar as Benign. ClinVar VariationId is 305452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CATSPER1	NM_053054.4 link	c.54C>T	p.Asn18Asn	synonymous_variant	Exon 1 of 12	ENST00000312106.6	NP_444282.3
CATSPER1	XM_047426337.1 link	c.54C>T	p.Asn18Asn	synonymous_variant	Exon 1 of 11		XP_047282293.1
CATSPER1	XM_047426338.1 link	c.54C>T	p.Asn18Asn	synonymous_variant	Exon 1 of 6		XP_047282294.1
CATSPER1	XR_002957121.2 link	n.154C>T		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER1	ENST00000312106.6 link	c.54C>T	p.Asn18Asn	synonymous_variant	Exon 1 of 12	1	NM_053054.4	ENSP00000309052.5

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30452

AN:

152074

Hom.:

3919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.245

AC:

61616

AN:

251422

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.0461

Gnomad AMR exome

AF:

0.445

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.249

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.243

AC:

354518

AN:

1461764

Hom.:

46131

Cov.:

AF XY:

0.238

AC XY:

172738

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0393

AC:

1317

AN:

33480

American (AMR)

AF:

0.432

AC:

19319

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5107

AN:

26136

East Asian (EAS)

AF:

0.223

AC:

8848

AN:

39700

South Asian (SAS)

AF:

0.102

AC:

8814

AN:

86256

European-Finnish (FIN)

AF:

0.299

AC:

15975

AN:

53362

Middle Eastern (MID)

AF:

0.158

AC:

912

AN:

5768

European-Non Finnish (NFE)

AF:

0.252

AC:

280231

AN:

1111944

Other (OTH)

AF:

0.232

AC:

13995

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

15503

31006

46510

62013

77516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9460

18920

28380

37840

47300

<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:

0.200

AC:

30460

AN:

152192

Hom.:

3921

Cov.:

AF XY:

0.204

AC XY:

15191

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0523

AC:

2173

AN:

41556

American (AMR)

AF:

0.333

AC:

5085

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

727

AN:

3470

East Asian (EAS)

AF:

0.231

AC:

1192

AN:

5166

South Asian (SAS)

AF:

0.113

AC:

547

AN:

4834

European-Finnish (FIN)

AF:

0.305

AC:

3230

AN:

10598

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16829

AN:

67966

Other (OTH)

AF:

0.189

AC:

398

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1174

2348

3521

4695

5869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.232

Hom.:

9024

Bravo

AF:

0.199

Asia WGS

AF:

0.188

AC:

653

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Spermatogenic failure 7

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.41

PhyloP100

0.11

PromoterAI

-0.030

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over