rs11809207

chr1-26194649-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198137.2(CATSPER4):c.459+761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,170 control chromosomes in the GnomAD database, including 2,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2938 hom., cov: 33)
• Consequence: CATSPER4 NM_198137.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

CATSPER4 (HGNC:23220): (cation channel sperm associated 4) Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CATSPER4	NM_198137.2	c.459+761G>A		intron_variant		ENST00000456354.7
CATSPER4	XM_011541432.4	c.459+761G>A		intron_variant
CATSPER4	XM_011541433.3	c.459+761G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CATSPER4	ENST00000456354.7	c.459+761G>A		intron_variant		1	NM_198137.2	P1
CATSPER4	ENST00000518899.5	c.459+761G>A		intron_variant, NMD_transcript_variant		1
CATSPER4	ENST00000338855.6	c.459+761G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28428 AN: 152052 Hom.: 2933 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 28447 AN: 152170 Hom.: 2938 Cov.: 33 AF XY: 0.181 AC XY: 13474 AN XY: 74412

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.192

Alfa AF: 0.181 Hom.: 3979

Bravo AF: 0.193

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.3
Dann	Benign	0.27

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: rs11809207; hg19: chr1-26521140;