chr22-39615268-G-A

Position:

• chr22-39615268-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021096.4(CACNA1I):​c.483-4042G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000789 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00079 (0 hom., cov: 32)
• Consequence: CACNA1I NM_021096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.54

Genes affected

CACNA1I (HGNC:1396): (calcium voltage-gated channel subunit alpha1 I) This gene encodes the pore-forming alpha subunit of a voltage gated calcium channel. The encoded protein is a member of a subfamily of calcium channels referred to as is a low voltage-activated, T-type, calcium channel. The channel encoded by this protein is characterized by a slower activation and inactivation compared to other T-type calcium channels. This protein may be involved in calcium signaling in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS2: High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1I	NM_021096.4	c.483-4042G>A		intron_variant		ENST00000402142.4
CACNA1I	NM_001003406.2	c.483-4042G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1I	ENST00000402142.4	c.483-4042G>A		intron_variant		1	NM_021096.4	A2
CACNA1I	ENST00000401624.5	c.483-4042G>A		intron_variant		1		P4
CACNA1I	ENST00000404898.5	c.483-4042G>A		intron_variant		1		A2
CACNA1I	ENST00000407673.5	c.483-4042G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

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

GnomAD4 genome AF: 0.000789 AC: 120 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54 AN XY: 74356

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.95

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: rs3788568; hg19: chr22-40011273;