rs5750870

Positions:

• chr22-39671635-G-A
• chr22-39671635-G-C
• chr22-39671635-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021096.4(CACNA1I):​c.4540-564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,958 control chromosomes in the GnomAD database, including 21,782 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 0.52 (21782 hom., cov: 32)
• Consequence: CACNA1I NM_021096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1I	NM_021096.4	c.4540-564G>A		intron_variant		ENST00000402142.4	NP_066919.2
CACNA1I	NM_001003406.2	c.4435-564G>A		intron_variant			NP_001003406.1
CACNA1I	XM_017029035.3	c.2686-564G>A		intron_variant			XP_016884524.1
CACNA1I	XM_017029036.2	c.2686-564G>A		intron_variant			XP_016884525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1I	ENST00000402142.4	c.4540-564G>A		intron_variant		1	NM_021096.4	ENSP00000385019	A2
CACNA1I	ENST00000401624.5	c.4540-564G>A		intron_variant		1		ENSP00000383887	P4
CACNA1I	ENST00000404898.5	c.4435-564G>A		intron_variant		1		ENSP00000384093	A2
CACNA1I	ENST00000407673.5	c.4435-564G>A		intron_variant		1		ENSP00000385680	A2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79628 AN: 151838 Hom.: 21751 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.525 AC: 79709 AN: 151958 Hom.: 21782 Cov.: 32 AF XY: 0.532 AC XY: 39512 AN XY: 74272

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.486

Alfa AF: 0.463 Hom.: 20153

Bravo AF: 0.530

Asia WGS AF: 0.713 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.8
DANN	Benign	0.81

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: rs5750870; hg19: chr22-40067640;