NM_000725.4:c.110G>A

Variant names:

• chr12-48823408-G-A
• rs145345389
• NM_000725.4:c.110G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000725.4(CACNB3):​c.110G>A​(p.Arg37Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,614,036 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: CACNB3 NM_000725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24784133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000725.4. 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
	CACNB3	NM_000725.4	MANE Select	c.110G>A	p.Arg37Gln	missense	Exon 2 of 13	NP_000716.2
	CACNB3	NM_001206916.2		c.107G>A	p.Arg36Gln	missense	Exon 2 of 13	NP_001193845.1	P54284-4
	CACNB3	NM_001206917.2		c.71G>A	p.Arg24Gln	missense	Exon 2 of 13	NP_001193846.1	P54284-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB3	ENST00000301050.7	TSL:1 MANE Select	c.110G>A	p.Arg37Gln	missense	Exon 2 of 13	ENSP00000301050.2	P54284-1
	CACNB3	ENST00000536187.6	TSL:2	c.107G>A	p.Arg36Gln	missense	Exon 2 of 13	ENSP00000444160.2	P54284-4
	CACNB3	ENST00000861431.1		c.110G>A	p.Arg37Gln	missense	Exon 2 of 13	ENSP00000531490.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251268 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000746 AC: 109 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62 AN XY: 727220

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000746 AC: 83 AN: 1111982

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.8	L
PhyloP100		6.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.099	T
Polyphen		0.50	P
Vest4		0.48
MVP		0.82
MPC		0.66
ClinPred		0.23	T
GERP RS		4.7
PromoterAI		0.00020	Neutral
Varity_R		0.30
gMVP		0.54
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs145345389; hg19: chr12-49217191;