12-48825355-C-G

Variant names:

• chr12-48825355-C-G
• rs11168751
• NM_000725.4:c.574-79C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000301050.7(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 ENST00000301050.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000301050.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB3	NM_000725.4	MANE Select	c.574-79C>G		intron	N/A	NP_000716.2
	CACNB3	NM_001206916.2		c.571-79C>G		intron	N/A	NP_001193845.1
	CACNB3	NM_001206917.2		c.535-79C>G		intron	N/A	NP_001193846.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB3	ENST00000301050.7	TSL:1 MANE Select	c.574-79C>G		intron	N/A	ENSP00000301050.2
	CACNB3	ENST00000536187.6	TSL:2	c.571-79C>G		intron	N/A	ENSP00000444160.2
	CACNB3	ENST00000540990.5	TSL:2	c.535-79C>G		intron	N/A	ENSP00000445495.1

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

African (AFR) AF: 0.326 AC: 10535 AN: 32358

American (AMR) AF: 0.107 AC: 4776 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4863 AN: 25622

East Asian (EAS) AF: 0.00119 AC: 47 AN: 39396

South Asian (SAS) AF: 0.200 AC: 17050 AN: 85038

European-Finnish (FIN) AF: 0.139 AC: 7424 AN: 53312

Middle Eastern (MID) AF: 0.188 AC: 1067 AN: 5674

European-Non Finnish (NFE) AF: 0.181 AC: 192379 AN: 1064876

Other (OTH) AF: 0.187 AC: 10963 AN: 58554

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

African (AFR) AF: 0.325 AC: 13455 AN: 41436

American (AMR) AF: 0.160 AC: 2451 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3472

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5168

South Asian (SAS) AF: 0.195 AC: 941 AN: 4818

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12276 AN: 67952

Other (OTH) AF: 0.210 AC: 442 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.34
PhyloP100		-0.78
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs11168751; hg19: chr12-49219138;