chr17-39177392-GGT-CGC

Variant names:

• chr17-39177392-GGT-CGC
• NM_000723.5:c.1288_1290delACCinsGCG
• CACNB1 p.Thr430Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000723.5(CACNB1):​c.1288_1290delACCinsGCG​(p.Thr430Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNB1 NM_000723.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1288_1290delACCinsGCG	p.Thr430Ala	missense	N/A	NP_000714.3
	CACNB1	NM_199247.3		c.1423_1425delACCinsGCG	p.Thr475Ala	missense	N/A	NP_954855.1	Q02641-2
	CACNB1	NM_199248.3		c.1288_1290delACCinsGCG	p.Thr430Ala	missense	N/A	NP_954856.1	Q02641-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB1	ENST00000394303.8	TSL:1 MANE Select	c.1288_1290delACCinsGCG	p.Thr430Ala	missense	N/A	ENSP00000377840.3	Q02641-1
	CACNB1	ENST00000344140.6	TSL:1	c.1423_1425delACCinsGCG	p.Thr475Ala	missense	N/A	ENSP00000345461.5	Q02641-2
	CACNB1	ENST00000394310.7	TSL:1	c.1288_1290delACCinsGCG	p.Thr430Ala	missense	N/A	ENSP00000377847.3	Q02641-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-37333645;