rs17633541

Positions:

• chr17-39173757-C-T

Variant summary

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

The NM_000723.5(CACNB1):​c.*1436G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,616 control chromosomes in the GnomAD database, including 190 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.

• Frequency:
  • Genomes: 𝑓 0.047 (190 hom., cov: 32)
  • Exomes 𝑓: 0.046 (0 hom.)
• Consequence: CACNB1 NM_000723.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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]

ENSG00000266101 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB1	NM_000723.5	c.*1436G>A		3_prime_UTR_variant	14/14	ENST00000394303.8	NP_000714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB1	ENST00000394303.8	c.*1436G>A		3_prime_UTR_variant	14/14	1	NM_000723.5	ENSP00000377840.3
ENSG00000266101	ENST00000579256.1	n.273+195C>T		intron_variant		4
CACNB1	ENST00000539338.6	n.*44G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7150 AN: 152152 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0605

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0462 AC: 16 AN: 346 Hom.: 0 Cov.: 0 AF XY: 0.0644 AC XY: 13 AN XY: 202

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0441

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0116

Gnomad4 NFE exome AF: 0.0702

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0470 AC: 7154 AN: 152270 Hom.: 190 Cov.: 32 AF XY: 0.0445 AC XY: 3316 AN XY: 74450

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0529 Hom.: 216

Bravo AF: 0.0516

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.72

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: rs17633541; hg19: chr17-37330010; COSMIC: COSV105228683; COSMIC: COSV105228683;