16-1220649-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021098.3(CACNA1H):c.6717C>T(p.Gly2239Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,603,900 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 9 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.206

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-1220649-C-T is Benign according to our data. Variant chr16-1220649-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1220649-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.206 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00203 (308/152048) while in subpopulation AFR AF= 0.0027 (112/41494). AF 95% confidence interval is 0.00229. There are 0 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 308 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.6717C>T	p.Gly2239Gly	synonymous_variant	Exon 35 of 35	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.6717C>T	p.Gly2239Gly	synonymous_variant	Exon 35 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.6699C>T	p.Gly2233Gly	synonymous_variant	Exon 33 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.6678C>T	p.Gly2226Gly	synonymous_variant	Exon 35 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000569107.5 link	c.2955C>T	p.Gly985Gly	synonymous_variant	Exon 17 of 17	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000564231.5 link	c.2907C>T	p.Gly969Gly	synonymous_variant	Exon 18 of 18	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000562079.5 link	c.2889C>T	p.Gly963Gly	synonymous_variant	Exon 17 of 17	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000639478.1 link	n.*1765C>T		non_coding_transcript_exon_variant	Exon 35 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*4535C>T		non_coding_transcript_exon_variant	Exon 35 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000639478.1 link	n.*1765C>T		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*4535C>T		3_prime_UTR_variant	Exon 35 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

307

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00233

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00120

AC:

268

AN:

223490

Hom.:

AF XY:

0.00122

AC XY:

151

AN XY:

123648

show subpopulations

Gnomad AFR exome

AF:

0.00254

Gnomad AMR exome

AF:

0.000306

Gnomad ASJ exome

AF:

0.00118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.000248

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.000539

GnomAD4 exome

AF:

0.00172

AC:

2495

AN:

1451852

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1215

AN XY:

721612

show subpopulations

Gnomad4 AFR exome

AF:

0.00232

Gnomad4 AMR exome

AF:

0.000300

Gnomad4 ASJ exome

AF:

0.000930

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00175

GnomAD4 genome

AF:

0.00203

AC:

308

AN:

152048

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00233

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00204

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 26, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CACNA1H: BP4, BP7 -

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Jan 27, 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

-0.72

CADD

Benign

3.4

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over