NM_021098.3:c.3650G>A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_021098.3(CACNA1H):c.3650G>A(p.Arg1217His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,597,748 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1217C) has been classified as Likely benign.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.3650G>A | p.Arg1217His | missense_variant | Exon 17 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
CACNA1H | ENST00000565831.6 | c.3650G>A | p.Arg1217His | missense_variant | Exon 16 of 33 | 1 | ENSP00000455840.1 | |||
CACNA1H | ENST00000638323.1 | c.3611G>A | p.Arg1204His | missense_variant | Exon 17 of 35 | 5 | ENSP00000492267.1 | |||
CACNA1H | ENST00000639478.1 | n.3650G>A | non_coding_transcript_exon_variant | Exon 17 of 35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*1563G>A | non_coding_transcript_exon_variant | Exon 17 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000640028.1 | n.*1563G>A | 3_prime_UTR_variant | Exon 17 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000637236.2 | n.-38G>A | upstream_gene_variant | 5 | ENSP00000492650.2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000176 AC: 4AN: 227338Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126212
GnomAD4 exome AF: 0.0000214 AC: 31AN: 1445418Hom.: 0 Cov.: 31 AF XY: 0.0000195 AC XY: 14AN XY: 719486
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74486
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.3650G>A (p.R1217H) alteration is located in exon 17 (coding exon 16) of the CACNA1H gene. This alteration results from a G to A substitution at nucleotide position 3650, causing the arginine (R) at amino acid position 1217 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV Benign:1
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Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at