12-48824661-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000725.4(CACNB3):​c.408-8C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,612,758 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 31 hom., cov: 30)
Exomes 𝑓: 0.00092 ( 21 hom. )

Consequence

CACNB3
NM_000725.4 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.002250
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.930
Variant links:
Genes affected
CACNB3 (HGNC:1403): (calcium voltage-gated channel auxiliary subunit beta 3) This gene encodes a regulatory beta subunit of the voltage-dependent calcium channel. Beta subunits are composed of five domains, which contribute to the regulation of surface expression and gating of calcium channels and may also play a role in the regulation of transcription factors and calcium transport. [provided by RefSeq, Oct 2011]

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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=-0.77).
BP6
Variant 12-48824661-C-A is Benign according to our data. Variant chr12-48824661-C-A is described in ClinVar as [Benign]. Clinvar id is 788882.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00953 (1450/152112) while in subpopulation AFR AF= 0.0333 (1381/41490). AF 95% confidence interval is 0.0318. There are 31 homozygotes in gnomad4. There are 660 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNB3NM_000725.4 linkuse as main transcriptc.408-8C>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000301050.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNB3ENST00000301050.7 linkuse as main transcriptc.408-8C>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_000725.4 P1P54284-1

Frequencies

GnomAD3 genomes
AF:
0.00951
AC:
1445
AN:
151994
Hom.:
31
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0333
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00341
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.00256
AC:
641
AN:
250814
Hom.:
14
AF XY:
0.00168
AC XY:
228
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.0365
Gnomad AMR exome
AF:
0.00119
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:
0.0000617
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000919
AC:
1343
AN:
1460646
Hom.:
21
Cov.:
32
AF XY:
0.000802
AC XY:
583
AN XY:
726644
show subpopulations
Gnomad4 AFR exome
AF:
0.0342
Gnomad4 AMR exome
AF:
0.00145
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:
0.0000279
Gnomad4 OTH exome
AF:
0.00164
GnomAD4 genome
AF:
0.00953
AC:
1450
AN:
152112
Hom.:
31
Cov.:
30
AF XY:
0.00888
AC XY:
660
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0333
Gnomad4 AMR
AF:
0.00340
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00664
Alfa
AF:
0.00300
Hom.:
3
Bravo
AF:
0.0103
Asia WGS
AF:
0.000866
AC:
4
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
8.4
DANN
Benign
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0022
dbscSNV1_RF
Benign
0.090
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: rs73298199; hg19: chr12-49218444; API