rs771719773
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_021098.3(CACNA1H):c.6244C>A(p.Arg2082Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,520,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 35)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00800
Genes affected
CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 16-1220176-C-A is Benign according to our data. Variant chr16-1220176-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 657180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.008 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1H | ENST00000348261.11 | c.6244C>A | p.Arg2082Arg | synonymous_variant | Exon 35 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
| CACNA1H | ENST00000565831.6 | c.6226C>A | p.Arg2076Arg | synonymous_variant | Exon 33 of 33 | 1 | ENSP00000455840.1 | |||
| CACNA1H | ENST00000638323.1 | c.6205C>A | p.Arg2069Arg | synonymous_variant | Exon 35 of 35 | 5 | ENSP00000492267.1 | |||
| CACNA1H | ENST00000569107.5 | c.2482C>A | p.Arg828Arg | synonymous_variant | Exon 17 of 17 | 1 | ENSP00000454990.2 | |||
| CACNA1H | ENST00000564231.5 | c.2434C>A | p.Arg812Arg | synonymous_variant | Exon 18 of 18 | 1 | ENSP00000457555.2 | |||
| CACNA1H | ENST00000562079.5 | c.2416C>A | p.Arg806Arg | synonymous_variant | Exon 17 of 17 | 1 | ENSP00000454581.2 | |||
| CACNA1H | ENST00000639478.1 | n.*1292C>A | non_coding_transcript_exon_variant | Exon 35 of 35 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.*4062C>A | non_coding_transcript_exon_variant | Exon 35 of 35 | 5 | ENSP00000491488.1 | ||||
| CACNA1H | ENST00000639478.1 | n.*1292C>A | 3_prime_UTR_variant | Exon 35 of 35 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.*4062C>A | 3_prime_UTR_variant | Exon 35 of 35 | 5 | ENSP00000491488.1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 35
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GnomAD4 exome AF: 7.31e-7 AC: 1AN: 1368002Hom.: 0 Cov.: 73 AF XY: 0.00 AC XY: 0AN XY: 673956
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GnomAD4 genome 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 35 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Jun 16, 2019
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Aug 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at