rs143055819

Variant names:

• chr17-67056092-C-A
• rs143055819
• NM_000727.4:c.490C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-67056092-C-A
• chr17-67056092-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000727.4(CACNG1):​c.490C>A​(p.Arg164Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000104 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: CACNG1 NM_000727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 4 publications found

Genes affected

CACNG1 (HGNC:1405): (calcium voltage-gated channel auxiliary subunit gamma 1) Voltage-dependent calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is part of skeletal muscle 1,4-dihydropyridine-sensitive calcium channels and is an integral membrane protein that plays a role in excitation-contraction coupling. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members that function as transmembrane AMPA receptor regulatory proteins (TARPs). [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14035478).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000727.4. 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
	CACNG1	NM_000727.4	MANE Select	c.490C>A	p.Arg164Ser	missense	Exon 4 of 4	NP_000718.1	Q06432

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG1	ENST00000226021.5	TSL:1 MANE Select	c.490C>A	p.Arg164Ser	missense	Exon 4 of 4	ENSP00000226021.3	Q06432
	CACNG1	ENST00000958687.1		c.586C>A	p.Arg196Ser	missense	Exon 5 of 5	ENSP00000628746.1

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 71 AN: 151976 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251146 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1461278 Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40 AN XY: 726950

African (AFR) AF: 0.00203 AC: 68 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52820

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.000199 AC: 12 AN: 60388

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74342

African (AFR) AF: 0.00145 AC: 60 AN: 41498

American (AMR) AF: 0.000720 AC: 11 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000156 Hom.: 0

Bravo AF: 0.000536

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.020	N
REVEL	Uncertain	0.45
Sift	Benign	0.45	T
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.54
MVP		0.71
MPC		1.1
ClinPred		0.12	T
GERP RS		4.8
Varity_R		0.41
gMVP		0.82
Mutation Taster		=29/71	disease causing

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: rs143055819; hg19: chr17-65052208;