rs11809207

Variant names:

• chr1-26194649-G-A
• rs11809207
• NM_198137.2:c.459+761G>A

Variant summary

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

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198137.2. 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
	CATSPER4	NM_198137.2	MANE Select	c.459+761G>A		intron	N/A	NP_937770.1	Q7RTX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER4	ENST00000456354.7	TSL:1 MANE Select	c.459+761G>A		intron	N/A	ENSP00000390423.3	Q7RTX7-1
	CATSPER4	ENST00000518899.5	TSL:1	n.459+761G>A		intron	N/A	ENSP00000429464.1	Q7RTX7-2
	CATSPER4	ENST00000338855.6	TSL:5	c.459+761G>A		intron	N/A	ENSP00000341006.2	J3KNU1

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

African (AFR) AF: 0.251 AC: 10412 AN: 41496

American (AMR) AF: 0.145 AC: 2215 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3464

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5188

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1569 AN: 10598

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12458 AN: 67998

Other (OTH) AF: 0.192 AC: 404 AN: 2102

Alfa AF: 0.182 Hom.: 9372

Bravo AF: 0.193

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.27
PhyloP100		0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11809207;

hg19: chr1-26521140;