GeneBe

rs17801265

Positions:

Variant summary

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

The NM_000719.7(CACNA1C):​c.916+3187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,198 control chromosomes in the GnomAD database, including 1,331 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 0.12 ( 1331 hom., cov: 32)

Consequence

CACNA1C
NM_000719.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.916+3187G>A intron_variant ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkuse as main transcriptc.916+3187G>A 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.916+3187G>A intron_variant 5 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.916+3187G>A intron_variant 1 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkuse as main transcriptc.1006+3187G>A intron_variant ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkuse as main transcriptc.916+3187G>A intron_variant 5 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkuse as main transcriptc.916+3187G>A intron_variant 5 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkuse as main transcriptc.1006+3187G>A intron_variant ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkuse as main transcriptc.916+3187G>A intron_variant 5 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkuse as main transcriptc.1006+3187G>A intron_variant ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkuse as main transcriptc.1006+3187G>A intron_variant ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkuse as main transcriptc.1006+3187G>A intron_variant ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkuse as main transcriptc.1006+3187G>A intron_variant ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkuse as main transcriptc.916+3187G>A intron_variant 5 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkuse as main transcriptc.916+3187G>A intron_variant ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkuse as main transcriptc.916+3187G>A intron_variant 1 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkuse as main transcriptc.916+3187G>A intron_variant ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkuse as main transcriptc.916+3187G>A intron_variant ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkuse as main transcriptc.916+3187G>A intron_variant ENSP00000507309.1 Q13936-19
CACNA1CENST00000682152.1 linkuse as main transcriptc.865+3187G>A intron_variant ENSP00000506759.1 A0A804HHT8
CACNA1CENST00000480911.6 linkuse as main transcriptn.916+3187G>A intron_variant 5 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
AF:
0.123
AC:
18675
AN:
152080
Hom.:
1327
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0807
Gnomad AMI
AF:
0.0822
Gnomad AMR
AF:
0.185
Gnomad ASJ
AF:
0.222
Gnomad EAS
AF:
0.0160
Gnomad SAS
AF:
0.117
Gnomad FIN
AF:
0.0789
Gnomad MID
AF:
0.161
Gnomad NFE
AF:
0.144
Gnomad OTH
AF:
0.148
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.123
AC:
18687
AN:
152198
Hom.:
1331
Cov.:
32
AF XY:
0.122
AC XY:
9105
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0806
Gnomad4 AMR
AF:
0.185
Gnomad4 ASJ
AF:
0.222
Gnomad4 EAS
AF:
0.0161
Gnomad4 SAS
AF:
0.116
Gnomad4 FIN
AF:
0.0789
Gnomad4 NFE
AF:
0.144
Gnomad4 OTH
AF:
0.146
Alfa
AF:
0.141
Hom.:
1145
Bravo
AF:
0.127
Asia WGS
AF:
0.0720
AC:
252
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
10
DANN
Benign
0.75

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: rs17801265; hg19: chr12-2598615; API