rs771718484
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_021098.3(CACNA1H):c.4065C>T(p.Gly1355Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,602,414 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.147
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 16-1210813-C-T is Benign according to our data. Variant chr16-1210813-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 460109.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BP7
Synonymous conserved (PhyloP=0.147 with no splicing effect.
BS2
High AC in GnomAdExome4 at 49 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1H | ENST00000348261.11 | c.4065C>T | p.Gly1355Gly | synonymous_variant | 21/35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
| CACNA1H | ENST00000565831.6 | c.4065C>T | p.Gly1355Gly | synonymous_variant | 20/33 | 1 | ENSP00000455840.1 | |||
| CACNA1H | ENST00000638323.1 | c.4026C>T | p.Gly1342Gly | synonymous_variant | 21/35 | 5 | ENSP00000492267.1 | |||
| CACNA1H | ENST00000569107.5 | c.288C>T | p.Gly96Gly | synonymous_variant | 4/17 | 1 | ENSP00000454990.2 | |||
| CACNA1H | ENST00000564231.5 | c.288C>T | p.Gly96Gly | synonymous_variant | 4/18 | 1 | ENSP00000457555.2 | |||
| CACNA1H | ENST00000562079.5 | c.288C>T | p.Gly96Gly | synonymous_variant | 4/17 | 1 | ENSP00000454581.2 | |||
| CACNA1H | ENST00000637236.2 | n.*35C>T | non_coding_transcript_exon_variant | 5/6 | 5 | ENSP00000492650.2 | ||||
| CACNA1H | ENST00000639478.1 | n.4065C>T | non_coding_transcript_exon_variant | 21/35 | 5 | ENSP00000491945.1 | ||||
| CACNA1H | ENST00000640028.1 | n.*1978C>T | non_coding_transcript_exon_variant | 21/35 | 5 | ENSP00000491488.1 | ||||
| CACNA1H | ENST00000637236.2 | n.*35C>T | 3_prime_UTR_variant | 5/6 | 5 | ENSP00000492650.2 | ||||
| CACNA1H | ENST00000640028.1 | n.*1978C>T | 3_prime_UTR_variant | 21/35 | 5 | ENSP00000491488.1 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000626 AC: 15AN: 239758Hom.: 0 AF XY: 0.0000837 AC XY: 11AN XY: 131376
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GnomAD4 exome AF: 0.0000338 AC: 49AN: 1450154Hom.: 0 Cov.: 39 AF XY: 0.0000305 AC XY: 22AN XY: 721956
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GnomAD4 genome 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1AN XY: 74396
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2016 | - - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 06, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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