chr17-50561537-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018896.5(CACNA1G):c.78G>A(p.Ser26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,538,344 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0026 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0034 ( 14 hom. )
Consequence
CACNA1G
NM_018896.5 synonymous
NM_018896.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.60
Genes affected
CACNA1G (HGNC:1394): (calcium voltage-gated channel subunit alpha1 G) Voltage-sensitive calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division, and cell death. This gene encodes a T-type, low-voltage activated calcium channel. The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Many alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2011]
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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=-0.47).
BP6
?
Variant 17-50561537-G-A is Benign according to our data. Variant chr17-50561537-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1302298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50561537-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.6 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00257 (391/151992) while in subpopulation NFE AF= 0.00361 (245/67902). AF 95% confidence interval is 0.00324. There are 2 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 391 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1G | NM_018896.5 | c.78G>A | p.Ser26= | synonymous_variant | 1/38 | ENST00000359106.10 | |
CACNA1G-AS1 | NR_038439.1 | n.181+391C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1G | ENST00000359106.10 | c.78G>A | p.Ser26= | synonymous_variant | 1/38 | 1 | NM_018896.5 | A2 | |
CACNA1G-AS1 | ENST00000505793.1 | n.181+391C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00257 AC: 391AN: 151872Hom.: 2 Cov.: 31
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GnomAD3 exomes AF: 0.00239 AC: 321AN: 134512Hom.: 1 AF XY: 0.00225 AC XY: 166AN XY: 73708
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GnomAD4 exome AF: 0.00336 AC: 4660AN: 1386352Hom.: 14 Cov.: 32 AF XY: 0.00326 AC XY: 2229AN XY: 684182
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GnomAD4 genome ? AF: 0.00257 AC: 391AN: 151992Hom.: 2 Cov.: 31 AF XY: 0.00262 AC XY: 195AN XY: 74296
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | CACNA1G-AS1: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
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