rs8101955

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000360228.11(CACNA1A):​c.1345+1928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,160 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5753 hom., cov: 32)

Consequence

CACNA1A
ENST00000360228.11 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960
Variant links:
Genes affected
CACNA1A (HGNC:1388): (calcium voltage-gated channel subunit alpha1 A) Voltage-dependent 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, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1ANM_001127222.2 linkuse as main transcriptc.1345+1928T>C intron_variant ENST00000360228.11 NP_001120694.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1AENST00000360228.11 linkuse as main transcriptc.1345+1928T>C intron_variant 1 NM_001127222.2 ENSP00000353362 O00555-8

Frequencies

GnomAD3 genomes
AF:
0.245
AC:
37180
AN:
152040
Hom.:
5726
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.444
Gnomad AMI
AF:
0.149
Gnomad AMR
AF:
0.194
Gnomad ASJ
AF:
0.190
Gnomad EAS
AF:
0.152
Gnomad SAS
AF:
0.246
Gnomad FIN
AF:
0.171
Gnomad MID
AF:
0.182
Gnomad NFE
AF:
0.158
Gnomad OTH
AF:
0.231
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.245
AC:
37262
AN:
152160
Hom.:
5753
Cov.:
32
AF XY:
0.243
AC XY:
18059
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.444
Gnomad4 AMR
AF:
0.194
Gnomad4 ASJ
AF:
0.190
Gnomad4 EAS
AF:
0.152
Gnomad4 SAS
AF:
0.246
Gnomad4 FIN
AF:
0.171
Gnomad4 NFE
AF:
0.158
Gnomad4 OTH
AF:
0.233
Alfa
AF:
0.171
Hom.:
4877
Bravo
AF:
0.256
Asia WGS
AF:
0.237
AC:
823
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
10
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8101955; hg19: chr19-13439130; API