rs11168751

Positions:

• chr12-48825355-C-G
• chr12-48825355-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000725.4(CACNB3):​c.574-79C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,561,444 control chromosomes in the GnomAD database, including 27,449 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.21 (3917 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23532 hom.)
• Consequence: CACNB3 NM_000725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB3	NM_000725.4	c.574-79C>G		intron_variant		ENST00000301050.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB3	ENST00000301050.7	c.574-79C>G		intron_variant		1	NM_000725.4	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31946 AN: 151906 Hom.: 3909 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.177 AC: 249104 AN: 1409420 Hom.: 23532 Cov.: 26 AF XY: 0.178 AC XY: 124989 AN XY: 703938

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.00119

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.210 AC: 31995 AN: 152024 Hom.: 3917 Cov.: 31 AF XY: 0.206 AC XY: 15334 AN XY: 74296

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.210

Alfa AF: 0.0938 Hom.: 148

Bravo AF: 0.212

Asia WGS AF: 0.110 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.34
BranchPoint Hunter		2.0

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

Other links and lift over

dbSNP: rs11168751; hg19: chr12-49219138;