16-1153321-CGGGCCGGGGGCGGAGGCGCTGGGGGCCGGGGCCG-C

Position:

• chr16-1153321-CGGGCCGGGGGCGGAGGCGCTGGGGGCCGGGGCCG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021098.3(CACNA1H):​c.-125_-92del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 139,872 control chromosomes in the GnomAD database, including 2,056 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2053 hom., cov: 21)
  • Exomes 𝑓: 0.092 (3 hom.)
• Consequence: CACNA1H NM_021098.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.12

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 -10 ACMG points.

• BP6: Variant 16-1153321-CGGGCCGGGGGCGGAGGCGCTGGGGGCCGGGGCCG-C is Benign according to our data. Variant chr16-1153321-CGGGCCGGGGGCGGAGGCGCTGGGGGCCGGGGCCG-C is described in ClinVar as [Benign]. Clinvar id is 1275909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1H	NM_021098.3	c.-125_-92del		5_prime_UTR_variant	1/35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11	c.-125_-92del		5_prime_UTR_variant	1/35	1	NM_021098.3	ENSP00000334198	P4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 22743 AN: 139256 Hom.: 2050 Cov.: 21

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0321

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.0918 AC: 56 AN: 610 Hom.: 3 AF XY: 0.0972 AC XY: 28 AN XY: 288

Gnomad4 SAS exome AF: 0.0908

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.163 AC: 22744 AN: 139262 Hom.: 2053 Cov.: 21 AF XY: 0.158 AC XY: 10689 AN XY: 67706

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.0734

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.171

Alfa AF: 0.146 Hom.: 232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1339556967; hg19: chr16-1203321;