17-50561582-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_018896.5(CACNA1G):ā€‹c.123G>Cā€‹(p.Pro41Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000832 in 1,561,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000089 ( 0 hom. )

Consequence

CACNA1G
NM_018896.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 17-50561582-G-C is Benign according to our data. Variant chr17-50561582-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 808292.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.43 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000894 (126/1409540) while in subpopulation NFE AF= 0.000111 (121/1088238). AF 95% confidence interval is 0.0000949. There are 0 homozygotes in gnomad4_exome. There are 61 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 126 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1GNM_018896.5 linkc.123G>C p.Pro41Pro synonymous_variant Exon 1 of 38 ENST00000359106.10 NP_061496.2 O43497-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1GENST00000359106.10 linkc.123G>C p.Pro41Pro synonymous_variant Exon 1 of 38 1 NM_018896.5 ENSP00000352011.5 O43497-1
CACNA1GENST00000507510.6 linkc.123G>C p.Pro41Pro synonymous_variant Exon 1 of 37 1 ENSP00000423112.2 O43497-12

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152034
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000374
AC:
6
AN:
160224
Hom.:
0
AF XY:
0.0000340
AC XY:
3
AN XY:
88348
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000149
Gnomad NFE exome
AF:
0.0000628
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000894
AC:
126
AN:
1409540
Hom.:
0
Cov.:
32
AF XY:
0.0000875
AC XY:
61
AN XY:
697048
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000446
Gnomad4 NFE exome
AF:
0.000111
Gnomad4 OTH exome
AF:
0.0000513
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
Asia WGS
AF:
0.000289
AC:
1
AN:
3474

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 01, 2021
CeGaT Center for Human Genetics Tuebingen
Significance: Likely 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
-0.59
CADD
Benign
6.9
DANN
Benign
0.90

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

LitVar

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

Other links and lift over

dbSNP: rs777628114; hg19: chr17-48638943; API