chr17-39175399-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000723.5(CACNB1):​c.1591G>A​(p.Gly531Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G531W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CACNB1
NM_000723.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38
Variant links:
Genes affected
CACNB1 (HGNC:1401): (calcium voltage-gated channel auxiliary subunit beta 1) The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11243221).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNB1NM_000723.5 linkc.1591G>A p.Gly531Arg missense_variant Exon 14 of 14 ENST00000394303.8 NP_000714.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNB1ENST00000394303.8 linkc.1591G>A p.Gly531Arg missense_variant Exon 14 of 14 1 NM_000723.5 ENSP00000377840.3 Q02641-1
CACNB1ENST00000539338.6 linkn.3710G>A non_coding_transcript_exon_variant Exon 12 of 12 1
ENSG00000266101ENST00000579256.1 linkn.274-1805C>T intron_variant Intron 1 of 1 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249202
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135282
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461850
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.065
T
Eigen
Benign
-0.062
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.13
N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.38
N
REVEL
Benign
0.22
Sift
Benign
0.39
T
Sift4G
Benign
0.45
T
Polyphen
0.42
B
Vest4
0.11
MutPred
0.24
Gain of solvent accessibility (P = 0.08);
MVP
0.46
MPC
0.91
ClinPred
0.36
T
GERP RS
5.7
Varity_R
0.19
gMVP
0.25

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: rs1443298887; hg19: chr17-37331652; API