rs775571017

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000719.7(CACNA1C):​c.2430G>A​(p.Thr810Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,577,292 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T810T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CACNA1C
NM_000719.7 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.87
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 Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 12-2585466-G-A is Benign according to our data. Variant chr12-2585466-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 526987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-2585466-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2.87 with no splicing effect.
BS2
High AC in GnomAdExome4 at 39 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/47 ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/47 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.2430G>A p.Thr810Thr synonymous_variant 17/475 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkuse as main transcriptc.2520G>A p.Thr840Thr synonymous_variant 17/50 ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/485 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/475 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkuse as main transcriptc.2595G>A p.Thr865Thr synonymous_variant 18/48 ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/491 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/481 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/485 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkuse as main transcriptc.2520G>A p.Thr840Thr synonymous_variant 17/47 ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkuse as main transcriptc.2520G>A p.Thr840Thr synonymous_variant 17/47 ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkuse as main transcriptc.2520G>A p.Thr840Thr synonymous_variant 17/47 ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkuse as main transcriptc.2520G>A p.Thr840Thr synonymous_variant 17/47 ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/481 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkuse as main transcriptc.2505G>A p.Thr835Thr synonymous_variant 18/485 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/481 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkuse as main transcriptc.2505G>A p.Thr835Thr synonymous_variant 18/47 ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/461 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/461 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/461 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/471 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/47 ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkuse as main transcriptc.2421G>A p.Thr807Thr synonymous_variant 17/47 ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkuse as main transcriptc.2430G>A p.Thr810Thr synonymous_variant 17/46 ENSP00000507309.1 Q13936-19
CACNA1CENST00000480911.6 linkuse as main transcriptn.*1037G>A non_coding_transcript_exon_variant 15/275 ENSP00000437936.2 F5H638
CACNA1CENST00000480911.6 linkuse as main transcriptn.*1037G>A 3_prime_UTR_variant 15/275 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000268
AC:
5
AN:
186368
Hom.:
0
AF XY:
0.0000499
AC XY:
5
AN XY:
100108
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000800
Gnomad FIN exome
AF:
0.0000555
Gnomad NFE exome
AF:
0.0000257
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
39
AN:
1425120
Hom.:
0
Cov.:
31
AF XY:
0.0000283
AC XY:
20
AN XY:
705760
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000262
Gnomad4 SAS exome
AF:
0.0000367
Gnomad4 FIN exome
AF:
0.0000393
Gnomad4 NFE exome
AF:
0.0000293
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 13, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.088
DANN
Benign
0.54

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

LitVar

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

Other links and lift over

dbSNP: rs775571017; hg19: chr12-2694632; API