chr11-66026326-G-A

Variant names:

• chr11-66026326-G-A
• rs1893316
• NM_053054.4:c.54C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053054.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER1	NM_053054.4	MANE Select	c.54C>T	p.Asn18Asn	synonymous	Exon 1 of 12	NP_444282.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER1	ENST00000312106.6	TSL:1 MANE Select	c.54C>T	p.Asn18Asn	synonymous	Exon 1 of 12	ENSP00000309052.5	Q8NEC5

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

GnomAD2 exomes AF: 0.245 AC: 61616 AN: 251422 AF XY: 0.235

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

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

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

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: 38 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16829 AN: 67966

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.232 Hom.: 9024

Bravo AF: 0.199

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Spermatogenic failure 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.11
PromoterAI		-0.030	Neutral
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: rs1893316; hg19: chr11-65793797; COSMIC: COSV56409037;