11-66020195-G-A

Position:

• chr11-66020195-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.2070C>T​(p.Ala690Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,442 control chromosomes in the GnomAD database, including 20,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2281 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18005 hom.)
• Consequence: CATSPER1 NM_053054.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.94

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=-1.01).
• BP6: Variant 11-66020195-G-A is Benign according to our data. Variant chr11-66020195-G-A is described in ClinVar as [Benign]. Clinvar id is 305419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER1	NM_053054.4	c.2070C>T	p.Ala690Ala	synonymous_variant	9/12	ENST00000312106.6	NP_444282.3
CATSPER1	XM_047426337.1	c.2070C>T	p.Ala690Ala	synonymous_variant	9/11		XP_047282293.1
CATSPER1	XR_002957121.2	n.2106C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER1	ENST00000312106.6	c.2070C>T	p.Ala690Ala	synonymous_variant	9/12	1	NM_053054.4	ENSP00000309052.5
CATSPER1	ENST00000529244.1	n.271C>T		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25854 AN: 151948 Hom.: 2281 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.152 AC: 38277 AN: 251116 Hom.: 3181 AF XY: 0.155 AC XY: 21115 AN XY: 135816

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.0968

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.154 AC: 224632 AN: 1461376 Hom.: 18005 Cov.: 36 AF XY: 0.155 AC XY: 112739 AN XY: 726998

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.170 AC: 25864 AN: 152066 Hom.: 2281 Cov.: 32 AF XY: 0.170 AC XY: 12643 AN XY: 74328

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.189

Alfa AF: 0.164 Hom.: 1486

Bravo AF: 0.169

Asia WGS AF: 0.167 AC: 584 AN: 3478

EpiCase AF: 0.170

EpiControl AF: 0.168

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

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	-1.0
CADD	Benign	0.14
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3829937; hg19: chr11-65787666; COSMIC: COSV56413908;