17-67046385-G-C

Variant names:

• chr17-67046385-G-C
• rs3785579
• NM_000727.4:c.229+1496G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000727.4(CACNG1):​c.229+1496G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,136 control chromosomes in the GnomAD database, including 1,262 homozygotes. 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 0.11 (1262 hom., cov: 32)
• Consequence: CACNG1 NM_000727.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG1	NM_000727.4	c.229+1496G>C		intron_variant	Intron 1 of 3	ENST00000226021.5	NP_000718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG1	ENST00000226021.5	c.229+1496G>C		intron_variant	Intron 1 of 3	1	NM_000727.4	ENSP00000226021.3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17364 AN: 152016 Hom.: 1257 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.114 AC: 17387 AN: 152136 Hom.: 1262 Cov.: 32 AF XY: 0.120 AC XY: 8893 AN XY: 74372

African (AFR) AF: 0.0269 AC: 1117 AN: 41524

American (AMR) AF: 0.156 AC: 2387 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0986 AC: 342 AN: 3470

East Asian (EAS) AF: 0.149 AC: 767 AN: 5154

South Asian (SAS) AF: 0.170 AC: 820 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2290 AN: 10590

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9267 AN: 67982

Other (OTH) AF: 0.120 AC: 254 AN: 2108

Alfa AF: 0.124 Hom.: 187

Bravo AF: 0.104

Asia WGS AF: 0.175 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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: rs3785579; hg19: chr17-65042501;