GeneBe

12-2237227-C-T

Position:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000719.7(CACNA1C):​c.477+116797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,012 control chromosomes in the GnomAD database, including 10,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 10219 hom., cov: 32)

Consequence

CACNA1C
NM_000719.7 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.486
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 12-2237227-C-T is Benign according to our data. Variant chr12-2237227-C-T is described in ClinVar as [Benign]. Clinvar id is 1168308.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.477+116797C>T intron_variant ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkuse as main transcriptc.477+116797C>T 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.477+116797C>T intron_variant 5 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.477+116797C>T intron_variant 1 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkuse as main transcriptc.567+116797C>T intron_variant ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkuse as main transcriptc.477+116797C>T intron_variant 5 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkuse as main transcriptc.477+116797C>T intron_variant 5 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkuse as main transcriptc.567+116797C>T intron_variant ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkuse as main transcriptc.477+116797C>T intron_variant 5 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkuse as main transcriptc.567+116797C>T intron_variant ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkuse as main transcriptc.567+116797C>T intron_variant ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkuse as main transcriptc.567+116797C>T intron_variant ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkuse as main transcriptc.567+116797C>T intron_variant ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkuse as main transcriptc.477+116797C>T intron_variant 5 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkuse as main transcriptc.477+116797C>T intron_variant ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkuse as main transcriptc.477+116797C>T intron_variant 1 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkuse as main transcriptc.477+116797C>T intron_variant ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkuse as main transcriptc.477+116797C>T intron_variant ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkuse as main transcriptc.477+116797C>T intron_variant ENSP00000507309.1 Q13936-19
CACNA1CENST00000682152.1 linkuse as main transcriptc.426+116797C>T intron_variant ENSP00000506759.1 A0A804HHT8
CACNA1CENST00000480911.6 linkuse as main transcriptn.477+116797C>T intron_variant 5 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
AF:
0.354
AC:
53760
AN:
151896
Hom.:
10224
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.478
Gnomad AMI
AF:
0.313
Gnomad AMR
AF:
0.286
Gnomad ASJ
AF:
0.294
Gnomad EAS
AF:
0.0507
Gnomad SAS
AF:
0.246
Gnomad FIN
AF:
0.319
Gnomad MID
AF:
0.231
Gnomad NFE
AF:
0.335
Gnomad OTH
AF:
0.327
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.354
AC:
53793
AN:
152012
Hom.:
10219
Cov.:
32
AF XY:
0.348
AC XY:
25883
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.478
Gnomad4 AMR
AF:
0.286
Gnomad4 ASJ
AF:
0.294
Gnomad4 EAS
AF:
0.0505
Gnomad4 SAS
AF:
0.247
Gnomad4 FIN
AF:
0.319
Gnomad4 NFE
AF:
0.335
Gnomad4 OTH
AF:
0.323
Alfa
AF:
0.314
Hom.:
15579
Bravo
AF:
0.353
Asia WGS
AF:
0.150
AC:
524
AN:
3478

ClinVar

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

Submissions by phenotype

Long QT syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 23, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.86
DANN
Benign
0.61

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: rs2159100; hg19: chr12-2346393; API