rs116613643

Variant names:

• chr17-39175529-C-T
• rs116613643
• NM_000723.5:c.1461G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39175529-C-T
• chr17-39175529-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000723.5(CACNB1):​c.1461G>A​(p.Arg487Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,613,870 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (49 hom.)
• Consequence: CACNB1 NM_000723.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.23
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 17-39175529-C-T is Benign according to our data. Variant chr17-39175529-C-T is described in ClinVar as Benign. ClinVar VariationId is 780422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00749 (1141/152262) while in subpopulation AFR AF = 0.0164 (683/41554). AF 95% confidence interval is 0.0154. There are 8 homozygotes in GnomAd4. There are 577 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

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.1461G>A	p.Arg487Arg	synonymous	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.1461G>A	p.Arg487Arg	synonymous	Exon 14 of 14	ENSP00000377840.3	Q02641-1
	CACNB1	ENST00000539338.6	TSL:1	n.3580G>A		non_coding_transcript_exon	Exon 12 of 12
	CACNB1	ENST00000910733.1		c.1596G>A	p.Arg532Arg	synonymous	Exon 14 of 14	ENSP00000580792.1

Frequencies

GnomAD3 genomes AF: 0.00749 AC: 1140 AN: 152144 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00492 AC: 1219 AN: 247936 AF XY: 0.00481

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.00676

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00291

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00322 AC: 4712 AN: 1461608 Hom.: 49 Cov.: 32 AF XY: 0.00349 AC XY: 2538 AN XY: 727122

African (AFR) AF: 0.0192 AC: 644 AN: 33476

American (AMR) AF: 0.00644 AC: 288 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 401 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00646 AC: 557 AN: 86246

European-Finnish (FIN) AF: 0.0000752 AC: 4 AN: 53214

Middle Eastern (MID) AF: 0.0461 AC: 266 AN: 5768

European-Non Finnish (NFE) AF: 0.00192 AC: 2130 AN: 1111974

Other (OTH) AF: 0.00697 AC: 421 AN: 60386

GnomAD4 genome AF: 0.00749 AC: 1141 AN: 152262 Hom.: 8 Cov.: 32 AF XY: 0.00775 AC XY: 577 AN XY: 74460

African (AFR) AF: 0.0164 AC: 683 AN: 41554

American (AMR) AF: 0.00771 AC: 118 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00807 AC: 39 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00285 AC: 194 AN: 68004

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.00392 Hom.: 8

Bravo AF: 0.00841

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00578

EpiControl AF: 0.00563

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		2.2
Mutation Taster		=97/3	polymorphism

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: rs116613643; hg19: chr17-37331782;