11-66026326-G-A

Position:

• chr11-66026326-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.110

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CATSPER1	NM_053054.4	c.54C>T	p.Asn18Asn	synonymous_variant	1/12	ENST00000312106.6	NP_444282.3
CATSPER1	XM_047426337.1	c.54C>T	p.Asn18Asn	synonymous_variant	1/11		XP_047282293.1
CATSPER1	XM_047426338.1	c.54C>T	p.Asn18Asn	synonymous_variant	1/6		XP_047282294.1
CATSPER1	XR_002957121.2	n.154C>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER1	ENST00000312106.6	c.54C>T	p.Asn18Asn	synonymous_variant	1/12	1	NM_053054.4	ENSP00000309052.5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30452 AN: 152074 Hom.: 3919 Cov.: 32

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

GnomAD3 exomes AF: 0.245 AC: 61616 AN: 251422 Hom.: 9228 AF XY: 0.235 AC XY: 31910 AN XY: 135888

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 SAS exome AF: 0.0998

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.: 38 AF XY: 0.238 AC XY: 172738 AN XY: 727194

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.200 AC: 30460 AN: 152192 Hom.: 3921 Cov.: 32 AF XY: 0.204 AC XY: 15191 AN XY: 74398

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.189

Alfa AF: 0.235 Hom.: 7533

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Spermatogenic failure 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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
DANN	Benign	0.41

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: rs1893316; hg19: chr11-65793797; COSMIC: COSV56409037;