rs122456135
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001256789.3(CACNA1F):c.2650C>T(p.Arg884*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,730 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. R884R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
CACNA1F
NM_001256789.3 stop_gained
NM_001256789.3 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 2.34
Publications
3 publications found
Genes affected
CACNA1F (HGNC:1393): (calcium voltage-gated channel subunit alpha1 F) This gene encodes a multipass transmembrane protein that functions as an alpha-1 subunit of the voltage-dependent calcium channel, which mediates the influx of calcium ions into the cell. The encoded protein forms a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Mutations in this gene can cause X-linked eye disorders, including congenital stationary night blindness type 2A, cone-rod dystropy, and Aland Island eye disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2013]
CACNA1F Gene-Disease associations (from GenCC):
- Aland island eye diseaseInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- inherited retinal dystrophyInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- congenital stationary night blindness 2AInheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- X-linked cone-rod dystrophy 3Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- cone-rod dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- congenital stationary night blindnessInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-49219344-G-A is Pathogenic according to our data. Variant chrX-49219344-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 11617.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1F | ENST00000323022.10 | c.2650C>T | p.Arg884* | stop_gained | Exon 21 of 48 | 1 | NM_001256789.3 | ENSP00000321618.6 | ||
| CACNA1F | ENST00000376265.2 | c.2683C>T | p.Arg895* | stop_gained | Exon 21 of 48 | 1 | ENSP00000365441.2 | |||
| CACNA1F | ENST00000376251.5 | c.2488C>T | p.Arg830* | stop_gained | Exon 21 of 48 | 1 | ENSP00000365427.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
22
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095730Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 361368 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1095730
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
361368
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26361
American (AMR)
AF:
AC:
0
AN:
35064
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19350
East Asian (EAS)
AF:
AC:
0
AN:
30165
South Asian (SAS)
AF:
AC:
0
AN:
53650
European-Finnish (FIN)
AF:
AC:
0
AN:
40334
Middle Eastern (MID)
AF:
AC:
0
AN:
3824
European-Non Finnish (NFE)
AF:
AC:
1
AN:
841018
Other (OTH)
AF:
AC:
0
AN:
45964
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
22
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Pathogenic:2
-
Clinical Genetics, Academic Medical Center
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
Congenital stationary night blindness 2A Pathogenic:1
Jul 01, 1998
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Congenital stationary night blindness Pathogenic:1
Jun 23, 2019
Sharon lab, Hadassah-Hebrew University Medical Center
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.