chr17-39176710-C-A

Variant names:

• chr17-39176710-C-A
• rs626657
• NM_000723.5:c.1332+640G>T

Variant summary

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

The NM_000723.5(CACNB1):​c.1332+640G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,154 control chromosomes in the GnomAD database, including 6,724 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 0.25 (6724 hom., cov: 32)
• Consequence: CACNB1 NM_000723.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 11 publications found

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:58562):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB1	NM_000723.5	c.1332+640G>T		intron_variant	Intron 13 of 13	ENST00000394303.8	NP_000714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB1	ENST00000394303.8	c.1332+640G>T		intron_variant	Intron 13 of 13	1	NM_000723.5	ENSP00000377840.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37274 AN: 152036 Hom.: 6708 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.245 AC: 37337 AN: 152154 Hom.: 6724 Cov.: 32 AF XY: 0.245 AC XY: 18225 AN XY: 74380

African (AFR) AF: 0.515 AC: 21379 AN: 41476

American (AMR) AF: 0.147 AC: 2249 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5164

South Asian (SAS) AF: 0.134 AC: 647 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1940 AN: 10590

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8834 AN: 68012

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.167 Hom.: 10293

Bravo AF: 0.253

Asia WGS AF: 0.218 AC: 756 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.29
PhyloP100		-2.1
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: rs626657; hg19: chr17-37332963;