16-1218001-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_021098.3(CACNA1H):c.5406C>T(p.Phe1802Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Publications

0 publications found

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 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)

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP7

Synonymous conserved (PhyloP=2.02 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 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.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.5421C>T	p.Phe1807Phe	synonymous_variant	Exon 31 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.5424C>T	p.Phe1808Phe	synonymous_variant	Exon 31 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.5388C>T	p.Phe1796Phe	synonymous_variant	Exon 31 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.5421C>T	p.Phe1807Phe	synonymous_variant	Exon 32 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.5367C>T	p.Phe1789Phe	synonymous_variant	Exon 32 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.5388C>T	p.Phe1796Phe	synonymous_variant	Exon 31 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.5349C>T	p.Phe1783Phe	synonymous_variant	Exon 31 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.5388C>T	p.Phe1796Phe	synonymous_variant	Exon 31 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.5406C>T	p.Phe1802Phe	synonymous_variant	Exon 32 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.5406C>T		non_coding_transcript_exon_variant	Exon 32 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.*1358C>T		non_coding_transcript_exon_variant	Exon 31 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.*487C>T		non_coding_transcript_exon_variant	Exon 32 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*3257C>T		non_coding_transcript_exon_variant	Exon 32 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*4850C>T		non_coding_transcript_exon_variant	Exon 30 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.*380C>T		non_coding_transcript_exon_variant	Exon 33 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.*265C>T		non_coding_transcript_exon_variant	Exon 32 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.*1018C>T		non_coding_transcript_exon_variant	Exon 33 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.*73C>T		non_coding_transcript_exon_variant	Exon 33 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.*73C>T		non_coding_transcript_exon_variant	Exon 33 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.5388C>T		non_coding_transcript_exon_variant	Exon 31 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.5406C>T		non_coding_transcript_exon_variant	Exon 32 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.5406C>T		non_coding_transcript_exon_variant	Exon 32 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.*522C>T		non_coding_transcript_exon_variant	Exon 32 of 35			ENSP00000518777.1
CACNA1H	ENST00000637236.3 link	n.*1358C>T		3_prime_UTR_variant	Exon 31 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.*487C>T		3_prime_UTR_variant	Exon 32 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*3257C>T		3_prime_UTR_variant	Exon 32 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*4850C>T		3_prime_UTR_variant	Exon 30 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.*380C>T		3_prime_UTR_variant	Exon 33 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.*265C>T		3_prime_UTR_variant	Exon 32 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.*1018C>T		3_prime_UTR_variant	Exon 33 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.*73C>T		3_prime_UTR_variant	Exon 33 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.*73C>T		3_prime_UTR_variant	Exon 33 of 36			ENSP00000518765.1
CACNA1H	ENST00000711488.1 link	n.*522C>T		3_prime_UTR_variant	Exon 32 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000438

AC:

AN:

228436

AF XY:

0.00000803

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.1

(source)

DANN

Benign

0.95

PhyloP100

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over