rs12934797

Variant names:

• chr16-1223982-C-G
• rs12934797
• ENST00000621827.2:n.*1122C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-1223982-C-G
• chr16-1223982-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000621827.2(CACNA1H):​n.*1122C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1H ENST00000621827.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684
• Publications: 3 publications found

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]

TPSG1 (HGNC:14134): (tryptase gamma 1) Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. There is uncertainty regarding the number of genes in this cluster. Currently four functional genes - alpha I, beta I, beta II and gamma I - have been identified. And beta I has an allelic variant named alpha II, beta II has an allelic variant beta III, also gamma I has an allelic variant gamma II. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha-tryptases predominant. This gene differs from other members of the tryptase gene family in that it has C-terminal hydrophobic domain, which may serve as a membrane anchor. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSG1	NM_012467.4	c.74-388G>C		intron_variant	Intron 2 of 5	ENST00000234798.5	NP_036599.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000621827.2	n.*1122C>G		non_coding_transcript_exon_variant	Exon 37 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000711486.1	n.*2451C>G		non_coding_transcript_exon_variant	Exon 37 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1	n.*2843C>G		non_coding_transcript_exon_variant	Exon 36 of 36			ENSP00000518776.1
CACNA1H	ENST00000564231.6	c.*2988C>G		3_prime_UTR_variant	Exon 35 of 35	1		ENSP00000457555.2
CACNA1H	ENST00000711438.1	c.*2988C>G		3_prime_UTR_variant	Exon 34 of 34			ENSP00000518754.1
CACNA1H	ENST00000621827.2	n.*1122C>G		3_prime_UTR_variant	Exon 37 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000711486.1	n.*2451C>G		3_prime_UTR_variant	Exon 37 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1	n.*2843C>G		3_prime_UTR_variant	Exon 36 of 36			ENSP00000518776.1
TPSG1	ENST00000234798.5	c.74-388G>C		intron_variant	Intron 2 of 5	1	NM_012467.4	ENSP00000234798.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149332 Hom.: 0 Cov.: 27

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 78792 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 39988

African (AFR) AF: 0.00 AC: 0 AN: 1686

American (AMR) AF: 0.00 AC: 0 AN: 1996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2436

East Asian (EAS) AF: 0.00 AC: 0 AN: 1816

South Asian (SAS) AF: 0.00 AC: 0 AN: 7734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52956

Other (OTH) AF: 0.00 AC: 0 AN: 5032

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149332 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 72748

African (AFR) AF: 0.00 AC: 0 AN: 40050

American (AMR) AF: 0.00 AC: 0 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5032

South Asian (SAS) AF: 0.00 AC: 0 AN: 4724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67532

Other (OTH) AF: 0.00 AC: 0 AN: 2042

Alfa AF: 0.00 Hom.: 2510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.41
PhyloP100		-0.68

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

Other links and lift over

dbSNP: rs12934797; hg19: chr16-1273982;