chr12-2605744-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_000719.7(CACNA1C):​c.3114G>A​(p.Leu1038Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1038L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CACNA1C
NM_000719.7 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.65
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-AS3 (HGNC:40117): (CACNA1C antisense RNA 3)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP7
Synonymous conserved (PhyloP=2.65 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1CNM_000719.7 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/47 ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/47 ENST00000399603.6 NP_001161095.1 Q13936-37

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1CENST00000399603.6 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/475 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkc.3264G>A p.Leu1088Leu synonymous_variant 25/50 ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/485 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/475 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkc.3279G>A p.Leu1093Leu synonymous_variant 25/48 ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkc.3174G>A p.Leu1058Leu synonymous_variant 25/491 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/481 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/485 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkc.3204G>A p.Leu1068Leu synonymous_variant 24/47 ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkc.3204G>A p.Leu1068Leu synonymous_variant 24/47 ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkc.3204G>A p.Leu1068Leu synonymous_variant 24/47 ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkc.3204G>A p.Leu1068Leu synonymous_variant 24/47 ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/481 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkc.3189G>A p.Leu1063Leu synonymous_variant 25/485 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkc.3174G>A p.Leu1058Leu synonymous_variant 25/481 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkc.3189G>A p.Leu1063Leu synonymous_variant 25/47 ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/461 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/461 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/461 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/471 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/47 ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkc.3105G>A p.Leu1035Leu synonymous_variant 24/47 ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkc.3114G>A p.Leu1038Leu synonymous_variant 24/46 ENSP00000507309.1 Q13936-19
CACNA1CENST00000480911.6 linkn.*1721G>A non_coding_transcript_exon_variant 22/275 ENSP00000437936.2 F5H638
CACNA1CENST00000480911.6 linkn.*1721G>A 3_prime_UTR_variant 22/275 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
11
DANN
Benign
0.86

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: rs114139824; hg19: chr12-2714910; API