rs2753325

Variant names:

• chr16-1211222-A-C
• rs2753325
• NM_021098.3:c.4278A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-1211222-A-C
• chr16-1211222-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021098.3(CACNA1H):​c.4278A>C​(p.Ser1426Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1426S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CACNA1H NM_021098.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-2.54 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3	c.4278A>C	p.Ser1426Ser	synonymous_variant	Exon 22 of 35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11	c.4278A>C	p.Ser1426Ser	synonymous_variant	Exon 22 of 35	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000565831.6	c.4278A>C	p.Ser1426Ser	synonymous_variant	Exon 21 of 33	1		ENSP00000455840.1
CACNA1H	ENST00000638323.1	c.4239A>C	p.Ser1413Ser	synonymous_variant	Exon 22 of 35	5		ENSP00000492267.1
CACNA1H	ENST00000569107.5	c.501A>C	p.Ser167Ser	synonymous_variant	Exon 5 of 17	1		ENSP00000454990.2
CACNA1H	ENST00000564231.5	c.501A>C	p.Ser167Ser	synonymous_variant	Exon 5 of 18	1		ENSP00000457555.2
CACNA1H	ENST00000562079.5	c.501A>C	p.Ser167Ser	synonymous_variant	Exon 5 of 17	1		ENSP00000454581.2
CACNA1H	ENST00000637236.2	n.*248A>C		non_coding_transcript_exon_variant	Exon 6 of 6	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1	n.4278A>C		non_coding_transcript_exon_variant	Exon 22 of 35	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1	n.*2191A>C		non_coding_transcript_exon_variant	Exon 22 of 35	5		ENSP00000491488.1
CACNA1H	ENST00000637236.2	n.*248A>C		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000492650.2
CACNA1H	ENST00000640028.1	n.*2191A>C		3_prime_UTR_variant	Exon 22 of 35	5		ENSP00000491488.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.080
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs2753325; hg19: chr16-1261222;