rs375169106

Variant names:

• chr16-1210666-G-A
• rs375169106
• NM_021098.3:c.4038+15G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-1210666-G-A
• chr16-1210666-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021098.3(CACNA1H):​c.4038+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,598,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: CACNA1H NM_021098.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680
• Publications: 0 publications found

Genes affected

CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]

CACNA1H Gene-Disease associations (from GenCC):

• hyperaldosteronism, familial, type IV

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• childhood absence epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy, childhood absence, susceptibility to, 6

  Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-1210666-G-A is Benign according to our data. Variant chr16-1210666-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2946253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3	c.4038+15G>A		intron_variant	Intron 20 of 34	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11	c.4038+15G>A		intron_variant	Intron 20 of 34	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000569107.6	c.4038+15G>A		intron_variant	Intron 20 of 33	1		ENSP00000454990.2
CACNA1H	ENST00000711493.1	c.4038+15G>A		intron_variant	Intron 20 of 33			ENSP00000518778.1
CACNA1H	ENST00000565831.7	c.4038+15G>A		intron_variant	Intron 20 of 33	1		ENSP00000455840.1
CACNA1H	ENST00000711450.1	c.4038+15G>A		intron_variant	Intron 20 of 34			ENSP00000518762.1
CACNA1H	ENST00000564231.6	c.4038+15G>A		intron_variant	Intron 20 of 34	1		ENSP00000457555.2
CACNA1H	ENST00000638323.1	c.3999+15G>A		intron_variant	Intron 20 of 34	5		ENSP00000492267.1
CACNA1H	ENST00000562079.6	c.4038+15G>A		intron_variant	Intron 20 of 33	1		ENSP00000454581.2
CACNA1H	ENST00000711438.1	c.3999+15G>A		intron_variant	Intron 20 of 33			ENSP00000518754.1
CACNA1H	ENST00000711482.1	c.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518771.1
CACNA1H	ENST00000711485.1	c.4038+15G>A		intron_variant	Intron 20 of 34			ENSP00000518774.1
CACNA1H	ENST00000711455.1	c.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518768.1
CACNA1H	ENST00000711483.1	c.4038+15G>A		intron_variant	Intron 20 of 34			ENSP00000518772.1
CACNA1H	ENST00000711456.1	c.4038+15G>A		intron_variant	Intron 20 of 33			ENSP00000518769.1
CACNA1H	ENST00000621827.2	n.4038+15G>A		intron_variant	Intron 20 of 36	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3	n.*8+15G>A		intron_variant	Intron 20 of 33	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1	n.4038+15G>A		intron_variant	Intron 20 of 34	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1	n.*1951+15G>A		intron_variant	Intron 20 of 34	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1	n.*3485+15G>A		intron_variant	Intron 19 of 33			ENSP00000518758.1
CACNA1H	ENST00000711448.1	n.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518760.1
CACNA1H	ENST00000711449.1	n.4038+15G>A		intron_variant	Intron 20 of 34			ENSP00000518761.1
CACNA1H	ENST00000711451.1	n.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518763.1
CACNA1H	ENST00000711452.1	n.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518764.1
CACNA1H	ENST00000711453.1	n.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518765.1
CACNA1H	ENST00000711484.1	n.4038+15G>A		intron_variant	Intron 20 of 34			ENSP00000518773.1
CACNA1H	ENST00000711486.1	n.4038+15G>A		intron_variant	Intron 20 of 36			ENSP00000518775.1
CACNA1H	ENST00000711487.1	n.4038+15G>A		intron_variant	Intron 20 of 35			ENSP00000518776.1
CACNA1H	ENST00000711488.1	n.4038+15G>A		intron_variant	Intron 20 of 34			ENSP00000518777.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000862 AC: 2 AN: 231952 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000221 AC: 32 AN: 1446350 Hom.: 0 Cov.: 38 AF XY: 0.0000236 AC XY: 17 AN XY: 719696

African (AFR) AF: 0.0000299 AC: 1 AN: 33406

American (AMR) AF: 0.0000225 AC: 1 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1110278

Other (OTH) AF: 0.0000333 AC: 2 AN: 60130

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152152 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.84
PhyloP100		-0.68

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: rs375169106; hg19: chr16-1260666; COSMIC: COSV62006759; COSMIC: COSV62006759;