GeneBe

rs1555884916

Positions:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_000719.7(CACNA1C):​c.3558+10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CACNA1C
NM_000719.7 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.390
Variant links:
Genes affected
CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 12-2608721-C-CT is Benign according to our data. Variant chr12-2608721-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 416851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.3558+10dupT intron_variant ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkuse as main transcriptc.3558+10dupT intron_variant ENST00000399603.6 NP_001161095.1 Q13936-37

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1CENST00000399603.6 linkuse as main transcriptc.3558+10dupT intron_variant 5 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.3558+10dupT intron_variant 1 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkuse as main transcriptc.3708+10dupT intron_variant ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkuse as main transcriptc.3558+10dupT intron_variant 5 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkuse as main transcriptc.3558+10dupT intron_variant 5 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkuse as main transcriptc.3723+10dupT intron_variant ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkuse as main transcriptc.3618+10dupT intron_variant 1 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkuse as main transcriptc.3558+10dupT intron_variant 5 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkuse as main transcriptc.3648+10dupT intron_variant ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkuse as main transcriptc.3648+10dupT intron_variant ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkuse as main transcriptc.3648+10dupT intron_variant ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkuse as main transcriptc.3648+10dupT intron_variant ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkuse as main transcriptc.3633+10dupT intron_variant 5 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkuse as main transcriptc.3618+10dupT intron_variant 1 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkuse as main transcriptc.3633+10dupT intron_variant ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkuse as main transcriptc.3558+10dupT intron_variant 1 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkuse as main transcriptc.3558+10dupT intron_variant ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkuse as main transcriptc.3549+10dupT intron_variant ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkuse as main transcriptc.3558+10dupT intron_variant ENSP00000507309.1 Q13936-19
CACNA1CENST00000480911.6 linkuse as main transcriptn.*2165+10dupT intron_variant 5 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461316
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726908
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 22, 2023- -
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs1555884916; hg19: chr12-2717887; API