22-39671635-G-T

Variant names:

• chr22-39671635-G-T
• rs5750870
• NM_021096.4:c.4540-564G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021096.4(CACNA1I):​c.4540-564G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CACNA1I NM_021096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 7 publications found

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]

CACNA1I Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with speech impairment and with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1I	NM_021096.4	c.4540-564G>T		intron_variant	Intron 26 of 36	ENST00000402142.4	NP_066919.2
CACNA1I	NM_001003406.2	c.4435-564G>T		intron_variant	Intron 25 of 35		NP_001003406.1
CACNA1I	XM_017029035.3	c.2686-564G>T		intron_variant	Intron 16 of 26		XP_016884524.1
CACNA1I	XM_017029036.2	c.2686-564G>T		intron_variant	Intron 16 of 26		XP_016884525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1I	ENST00000402142.4	c.4540-564G>T		intron_variant	Intron 26 of 36	1	NM_021096.4	ENSP00000385019.3
CACNA1I	ENST00000404898.5	c.4435-564G>T		intron_variant	Intron 25 of 35	1		ENSP00000384093.1
CACNA1I	ENST00000401624.5	c.4540-564G>T		intron_variant	Intron 26 of 35	1		ENSP00000383887.1
CACNA1I	ENST00000407673.5	c.4435-564G>T		intron_variant	Intron 25 of 34	1		ENSP00000385680.1

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.83
PhyloP100		0.081

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: rs5750870; hg19: chr22-40067640;