NM_018896.5:c.78G>A

Variant names:

• chr17-50561537-G-A
• rs577987926
• NM_018896.5:c.78G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018896.5(CACNA1G):​c.78G>A​(p.Ser26Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,538,344 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0034 (14 hom.)
• Consequence: CACNA1G NM_018896.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.60
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-50561537-G-A is Benign according to our data. Variant chr17-50561537-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1302298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.6 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00257 (391/151992) while in subpopulation NFE AF = 0.00361 (245/67902). AF 95% confidence interval is 0.00324. There are 2 homozygotes in GnomAd4. There are 195 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018896.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1G	NM_018896.5	MANE Select	c.78G>A	p.Ser26Ser	synonymous	Exon 1 of 38	NP_061496.2
	CACNA1G	NM_198377.3		c.78G>A	p.Ser26Ser	synonymous	Exon 1 of 37	NP_938191.2	O43497-20
	CACNA1G	NM_198396.3		c.78G>A	p.Ser26Ser	synonymous	Exon 1 of 36	NP_938406.1	O43497-33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1G	ENST00000359106.10	TSL:1 MANE Select	c.78G>A	p.Ser26Ser	synonymous	Exon 1 of 38	ENSP00000352011.5	O43497-1
	CACNA1G	ENST00000507336.5	TSL:1	c.78G>A	p.Ser26Ser	synonymous	Exon 1 of 37	ENSP00000420918.1	O43497-20
	CACNA1G	ENST00000507510.6	TSL:1	c.78G>A	p.Ser26Ser	synonymous	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 151872 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000508

Gnomad AMI AF: 0.00441

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00361

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00239 AC: 321 AN: 134512 AF XY: 0.00225

Gnomad AFR exome AF: 0.000614

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.00366

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00336 AC: 4660 AN: 1386352 Hom.: 14 Cov.: 32 AF XY: 0.00326 AC XY: 2229 AN XY: 684182

African (AFR) AF: 0.000634 AC: 20 AN: 31542

American (AMR) AF: 0.00104 AC: 37 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.0000398 AC: 1 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.000316 AC: 25 AN: 79198

European-Finnish (FIN) AF: 0.0118 AC: 444 AN: 37762

Middle Eastern (MID) AF: 0.000792 AC: 4 AN: 5048

European-Non Finnish (NFE) AF: 0.00366 AC: 3948 AN: 1078456

Other (OTH) AF: 0.00313 AC: 181 AN: 57798

GnomAD4 genome AF: 0.00257 AC: 391 AN: 151992 Hom.: 2 Cov.: 31 AF XY: 0.00262 AC XY: 195 AN XY: 74296

African (AFR) AF: 0.000506 AC: 21 AN: 41468

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00361 AC: 245 AN: 67902

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00291 Hom.: 3

Bravo AF: 0.00203

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.7
DANN	Benign	0.96
PhyloP100		-2.6
PromoterAI		-0.042	Neutral
Mutation Taster		=97/3	polymorphism

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: rs577987926; hg19: chr17-48638898;