17-50560854-G-A

Position:

• chr17-50560854-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018896.5(CACNA1G):​c.-606G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 151,718 control chromosomes in the GnomAD database, including 818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (818 hom., cov: 33)
• Consequence: CACNA1G NM_018896.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.864

Genes affected

CACNA1G (HGNC:1394): (calcium voltage-gated channel subunit alpha1 G) Voltage-sensitive calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division, and cell death. This gene encodes a T-type, low-voltage activated calcium channel. The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Many alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2011]

CACNA1G-AS1 (HGNC:27377): (CACNA1G antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 17-50560854-G-A is Benign according to our data. Variant chr17-50560854-G-A is described in ClinVar as [Benign]. Clinvar id is 1271024.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1G	NM_018896.5	c.-606G>A		5_prime_UTR_variant	1/38	ENST00000359106.10
CACNA1G-AS1	NR_038439.1	n.181+1074C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1G	ENST00000359106.10	c.-606G>A		5_prime_UTR_variant	1/38	1	NM_018896.5	A2
CACNA1G-AS1	ENST00000505793.1	n.181+1074C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15148 AN: 151618 Hom.: 817 Cov.: 33

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0999 AC: 15159 AN: 151718 Hom.: 818 Cov.: 33 AF XY: 0.0991 AC XY: 7349 AN XY: 74126

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0192

Gnomad4 SAS AF: 0.0751

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0411 Hom.: 27

Bravo AF: 0.100

Asia WGS AF: 0.0440 AC: 152 AN: 3432

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62059718; hg19: chr17-48638215;