rs57687113

Variant names:

• chr16-1217915-G-A
• rs57687113
• NM_021098.3:c.5324-4G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-1217915-G-A
• chr16-1217915-G-C
• chr16-1217915-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_021098.3(CACNA1H):​c.5324-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,598,276 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00060 (8 hom.)
• Consequence: CACNA1H NM_021098.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001647
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.23

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-1217915-G-A is Benign according to our data. Variant chr16-1217915-G-A is described in ClinVar as [Benign]. Clinvar id is 529687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1217915-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00515 (785/152320) while in subpopulation AFR AF= 0.0173 (721/41572). AF 95% confidence interval is 0.0163. There are 4 homozygotes in gnomad4. There are 368 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 785 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3	c.5324-4G>A		splice_region_variant, intron_variant	Intron 31 of 34	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11	c.5324-4G>A		splice_region_variant, intron_variant	Intron 31 of 34	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000565831.6	c.5306-4G>A		splice_region_variant, intron_variant	Intron 29 of 32	1		ENSP00000455840.1
CACNA1H	ENST00000638323.1	c.5285-4G>A		splice_region_variant, intron_variant	Intron 31 of 34	5		ENSP00000492267.1
CACNA1H	ENST00000569107.5	c.1562-4G>A		splice_region_variant, intron_variant	Intron 13 of 16	1		ENSP00000454990.2
CACNA1H	ENST00000564231.5	c.1547-4G>A		splice_region_variant, intron_variant	Intron 14 of 17	1		ENSP00000457555.2
CACNA1H	ENST00000562079.5	c.1529-4G>A		splice_region_variant, intron_variant	Intron 13 of 16	1		ENSP00000454581.2
CACNA1H	ENST00000639478.1	n.*405-4G>A		splice_region_variant, intron_variant	Intron 31 of 34	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1	n.*3175-4G>A		splice_region_variant, intron_variant	Intron 31 of 34	5		ENSP00000491488.1

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 785 AN: 152202 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00113 AC: 253 AN: 223638 Hom.: 3 AF XY: 0.000833 AC XY: 102 AN XY: 122376

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.000772

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000609

Gnomad SAS exome AF: 0.000144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000602

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000600 AC: 867 AN: 1445956 Hom.: 8 Cov.: 32 AF XY: 0.000496 AC XY: 356 AN XY: 717926

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000774

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00515 AC: 785 AN: 152320 Hom.: 4 Cov.: 34 AF XY: 0.00494 AC XY: 368 AN XY: 74492

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00250 Hom.: 2

Bravo AF: 0.00623

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV Benign:1

Aug 04, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.85
CADD	Benign	0.070
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0020
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: rs57687113; hg19: chr16-1267915;