chr17-39175092-A-T

Position:

• chr17-39175092-A-T

Variant summary

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

The NM_000723.5(CACNB1):​c.*101T>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 0.16 in 965,660 control chromosomes in the GnomAD database, including 13,569 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 0.20 (3401 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10168 hom.)
• Consequence: CACNB1 NM_000723.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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]

CACNB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB1	NM_000723.5	c.*101T>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.*101T>A		3_prime_UTR_variant	14/14	1	NM_000723.5	ENSP00000377840.3
CACNB1	ENST00000539338.6	n.4017T>A		non_coding_transcript_exon_variant	12/12	1
ENSG00000266101	ENST00000579256.1	n.273+1530A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30084 AN: 151854 Hom.: 3406 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.153 AC: 124741 AN: 813688 Hom.: 10168 Cov.: 11 AF XY: 0.152 AC XY: 63572 AN XY: 417018

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.198 AC: 30108 AN: 151972 Hom.: 3401 Cov.: 32 AF XY: 0.198 AC XY: 14687 AN XY: 74244

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0801 Hom.: 107

Bravo AF: 0.196

Asia WGS AF: 0.211 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.2
DANN	Benign	0.83

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: rs523516; hg19: chr17-37331345; COSMIC: COSV59999654; COSMIC: COSV59999654;