rs16537

Variant names:

• chr17-39196025-C-T
• rs16537
• NM_000723.5:c.85-1055G>A

Variant summary

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

The NM_000723.5(CACNB1):​c.85-1055G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,230 control chromosomes in the GnomAD database, including 1,074 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 0.11 (1074 hom., cov: 32)
• Consequence: CACNB1 NM_000723.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB1	NM_000723.5	c.85-1055G>A		intron_variant	Intron 1 of 13	ENST00000394303.8	NP_000714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB1	ENST00000394303.8	c.85-1055G>A		intron_variant	Intron 1 of 13	1	NM_000723.5	ENSP00000377840.3
CACNB1	ENST00000344140.6	c.85-1055G>A		intron_variant	Intron 1 of 12	1		ENSP00000345461.5
CACNB1	ENST00000394310.7	c.85-1055G>A		intron_variant	Intron 1 of 12	1		ENSP00000377847.3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16098 AN: 152112 Hom.: 1077 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0550

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16099 AN: 152230 Hom.: 1074 Cov.: 32 AF XY: 0.103 AC XY: 7674 AN XY: 74420

Gnomad4 AFR AF: 0.0497

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.117

Alfa AF: 0.142 Hom.: 1603

Bravo AF: 0.107

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.71

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: rs16537; hg19: chr17-37352278;