chr16-1220439-G-A

Position:

• chr16-1220439-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021098.3(CACNA1H):​c.6507G>A​(p.Lys2169Lys) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1H NM_021098.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-1220439-G-A is Benign according to our data. Variant chr16-1220439-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1H	NM_021098.3	c.6507G>A	p.Lys2169Lys	synonymous_variant	35/35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11	c.6507G>A	p.Lys2169Lys	synonymous_variant	35/35	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000565831.6	c.6489G>A	p.Lys2163Lys	synonymous_variant	33/33	1		ENSP00000455840.1
CACNA1H	ENST00000638323.1	c.6468G>A	p.Lys2156Lys	synonymous_variant	35/35	5		ENSP00000492267.1
CACNA1H	ENST00000569107.5	c.2745G>A	p.Lys915Lys	synonymous_variant	17/17	1		ENSP00000454990.2
CACNA1H	ENST00000564231.5	c.2697G>A	p.Lys899Lys	synonymous_variant	18/18	1		ENSP00000457555.2
CACNA1H	ENST00000562079.5	c.2679G>A	p.Lys893Lys	synonymous_variant	17/17	1		ENSP00000454581.2
CACNA1H	ENST00000639478.1	n.*1555G>A		non_coding_transcript_exon_variant	35/35	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1	n.*4325G>A		non_coding_transcript_exon_variant	35/35	5		ENSP00000491488.1
CACNA1H	ENST00000639478.1	n.*1555G>A		3_prime_UTR_variant	35/35	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1	n.*4325G>A		3_prime_UTR_variant	35/35	5		ENSP00000491488.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1385924 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 684906

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.6
DANN	Benign	0.65

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: rs1555521007; hg19: chr16-1270439;