rs553500083

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_000719.7(CACNA1C):​c.6034C>A​(p.Arg2012Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CACNA1C
NM_000719.7 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.32
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]
CACNA1C-AS1 (HGNC:40119): (CACNA1C antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 12-2688696-C-A is Benign according to our data. Variant chr12-2688696-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1106870.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.32 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1CNM_000719.7 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 ENST00000399603.6 NP_001161095.1 Q13936-37

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1CENST00000399603.6 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 5 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 1 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkc.6373C>A p.Arg2125Arg synonymous_variant Exon 49 of 50 ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkc.6247C>A p.Arg2083Arg synonymous_variant Exon 47 of 48 5 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkc.6214C>A p.Arg2072Arg synonymous_variant Exon 46 of 47 5 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkc.6199C>A p.Arg2067Arg synonymous_variant Exon 47 of 48 ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkc.6178C>A p.Arg2060Arg synonymous_variant Exon 48 of 49 1 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkc.6157C>A p.Arg2053Arg synonymous_variant Exon 46 of 47 1 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkc.6139C>A p.Arg2047Arg synonymous_variant Exon 47 of 48 1 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkc.6139C>A p.Arg2047Arg synonymous_variant Exon 47 of 48 5 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkc.6124C>A p.Arg2042Arg synonymous_variant Exon 46 of 47 ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkc.6124C>A p.Arg2042Arg synonymous_variant Exon 46 of 47 ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkc.6124C>A p.Arg2042Arg synonymous_variant Exon 46 of 47 ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkc.6124C>A p.Arg2042Arg synonymous_variant Exon 46 of 47 ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkc.6118C>A p.Arg2040Arg synonymous_variant Exon 47 of 48 1 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkc.6109C>A p.Arg2037Arg synonymous_variant Exon 47 of 48 5 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkc.6094C>A p.Arg2032Arg synonymous_variant Exon 47 of 48 1 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkc.6091C>A p.Arg2031Arg synonymous_variant Exon 46 of 47 1 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkc.6091C>A p.Arg2031Arg synonymous_variant Exon 46 of 47 1 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkc.6091C>A p.Arg2031Arg synonymous_variant Exon 46 of 47 1 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkc.6085C>A p.Arg2029Arg synonymous_variant Exon 46 of 47 1 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkc.6076C>A p.Arg2026Arg synonymous_variant Exon 46 of 47 ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkc.6058C>A p.Arg2020Arg synonymous_variant Exon 45 of 46 1 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkc.6058C>A p.Arg2020Arg synonymous_variant Exon 45 of 46 1 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkc.6052C>A p.Arg2018Arg synonymous_variant Exon 45 of 46 1 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 1 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 1 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 1 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 1 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkc.6034C>A p.Arg2012Arg synonymous_variant Exon 46 of 47 ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkc.6025C>A p.Arg2009Arg synonymous_variant Exon 46 of 47 ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkc.6001C>A p.Arg2001Arg synonymous_variant Exon 45 of 46 ENSP00000507309.1 Q13936-19

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Long QT syndrome Benign:1
Aug 07, 2020
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
8.2
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-2797862; API