16-1211222-A-G
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_021098.3(CACNA1H):c.4278A>G(p.Ser1426Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,612,144 control chromosomes in the GnomAD database, including 304,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.66 ( 33517 hom., cov: 34)
Exomes 𝑓: 0.61 ( 271398 hom. )
Consequence
CACNA1H
NM_021098.3 synonymous
NM_021098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.54
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 16-1211222-A-G is Benign according to our data. Variant chr16-1211222-A-G is described in ClinVar as [Benign]. Clinvar id is 585643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1211222-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.54 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.4278A>G | p.Ser1426Ser | synonymous_variant | Exon 22 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
CACNA1H | ENST00000565831.6 | c.4278A>G | p.Ser1426Ser | synonymous_variant | Exon 21 of 33 | 1 | ENSP00000455840.1 | |||
CACNA1H | ENST00000638323.1 | c.4239A>G | p.Ser1413Ser | synonymous_variant | Exon 22 of 35 | 5 | ENSP00000492267.1 | |||
CACNA1H | ENST00000569107.5 | c.501A>G | p.Ser167Ser | synonymous_variant | Exon 5 of 17 | 1 | ENSP00000454990.2 | |||
CACNA1H | ENST00000564231.5 | c.501A>G | p.Ser167Ser | synonymous_variant | Exon 5 of 18 | 1 | ENSP00000457555.2 | |||
CACNA1H | ENST00000562079.5 | c.501A>G | p.Ser167Ser | synonymous_variant | Exon 5 of 17 | 1 | ENSP00000454581.2 | |||
CACNA1H | ENST00000637236.2 | n.*248A>G | non_coding_transcript_exon_variant | Exon 6 of 6 | 5 | ENSP00000492650.2 | ||||
CACNA1H | ENST00000639478.1 | n.4278A>G | non_coding_transcript_exon_variant | Exon 22 of 35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*2191A>G | non_coding_transcript_exon_variant | Exon 22 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000637236.2 | n.*248A>G | 3_prime_UTR_variant | Exon 6 of 6 | 5 | ENSP00000492650.2 | ||||
CACNA1H | ENST00000640028.1 | n.*2191A>G | 3_prime_UTR_variant | Exon 22 of 35 | 5 | ENSP00000491488.1 |
Frequencies
GnomAD3 genomes AF: 0.658 AC: 99933AN: 151876Hom.: 33488 Cov.: 34
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GnomAD3 exomes AF: 0.652 AC: 162023AN: 248452Hom.: 54010 AF XY: 0.641 AC XY: 86570AN XY: 135074
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GnomAD4 exome AF: 0.605 AC: 883958AN: 1460150Hom.: 271398 Cov.: 54 AF XY: 0.603 AC XY: 438145AN XY: 726402
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GnomAD4 genome AF: 0.658 AC: 100007AN: 151994Hom.: 33517 Cov.: 34 AF XY: 0.665 AC XY: 49444AN XY: 74306
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Apr 20, 2017
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Jan 16, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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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