rs876657433
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001128840.3(CACNA1D):c.450T>C(p.Pro150Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,922 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CACNA1D
NM_001128840.3 synonymous
NM_001128840.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.63
Publications
0 publications found
Genes affected
CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
CACNA1D Gene-Disease associations (from GenCC):
- aldosterone-producing adenoma with seizures and neurological abnormalitiesInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- complex neurodevelopmental disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- sinoatrial node dysfunction and deafnessInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 3-53501687-T-C is Benign according to our data. Variant chr3-53501687-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 227201.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.63 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001128840.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNA1D | MANE Plus Clinical | c.450T>C | p.Pro150Pro | synonymous | Exon 3 of 49 | NP_000711.1 | Q01668-2 | ||
| CACNA1D | MANE Select | c.450T>C | p.Pro150Pro | synonymous | Exon 3 of 48 | NP_001122312.1 | Q01668-1 | ||
| CACNA1D | c.450T>C | p.Pro150Pro | synonymous | Exon 3 of 46 | NP_001122311.1 | Q01668-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNA1D | TSL:1 MANE Plus Clinical | c.450T>C | p.Pro150Pro | synonymous | Exon 3 of 49 | ENSP00000288139.3 | Q01668-2 | ||
| CACNA1D | TSL:1 MANE Select | c.450T>C | p.Pro150Pro | synonymous | Exon 3 of 48 | ENSP00000288133.5 | Q01668-1 | ||
| CACNA1D | TSL:1 | c.450T>C | p.Pro150Pro | synonymous | Exon 3 of 49 | ENSP00000418014.2 | H0Y879 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1444922Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1AN XY: 720004 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1444922
Hom.:
Cov.:
26
AF XY:
AC XY:
1
AN XY:
720004
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33136
American (AMR)
AF:
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26036
East Asian (EAS)
AF:
AC:
0
AN:
39588
South Asian (SAS)
AF:
AC:
0
AN:
85914
European-Finnish (FIN)
AF:
AC:
0
AN:
53008
Middle Eastern (MID)
AF:
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1097052
Other (OTH)
AF:
AC:
0
AN:
59732
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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10
<30
30-35
35-40
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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