17-39175092-A-T

Variant names:

• chr17-39175092-A-T
• rs523516
• NM_000723.5:c.*101T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000723.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB1	NM_000723.5	MANE Select	c.*101T>A		3_prime_UTR	Exon 14 of 14	NP_000714.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB1	ENST00000394303.8	TSL:1 MANE Select	c.*101T>A		3_prime_UTR	Exon 14 of 14	ENSP00000377840.3	Q02641-1
	CACNB1	ENST00000539338.6	TSL:1	n.4017T>A		non_coding_transcript_exon	Exon 12 of 12
	CACNB1	ENST00000910733.1		c.*101T>A		3_prime_UTR	Exon 14 of 14	ENSP00000580792.1

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

African (AFR) AF: 0.325 AC: 6442 AN: 19824

American (AMR) AF: 0.103 AC: 2845 AN: 27636

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 2183 AN: 16402

East Asian (EAS) AF: 0.189 AC: 6844 AN: 36304

South Asian (SAS) AF: 0.153 AC: 8952 AN: 58628

European-Finnish (FIN) AF: 0.191 AC: 8817 AN: 46264

Middle Eastern (MID) AF: 0.139 AC: 373 AN: 2688

European-Non Finnish (NFE) AF: 0.145 AC: 82297 AN: 568082

Other (OTH) AF: 0.158 AC: 5988 AN: 37860

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

African (AFR) AF: 0.319 AC: 13190 AN: 41388

American (AMR) AF: 0.128 AC: 1959 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1143 AN: 5150

South Asian (SAS) AF: 0.157 AC: 757 AN: 4816

European-Finnish (FIN) AF: 0.192 AC: 2036 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10017 AN: 67950

Other (OTH) AF: 0.175 AC: 369 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.2
DANN	Benign	0.83
PhyloP100		0.42
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: rs523516; hg19: chr17-37331345; COSMIC: COSV59999654; COSMIC: COSV59999654;