chr19-53991509-T-C

Variant names:

• chr19-53991509-T-C
• rs251850
• NR_102308.2:n.49+312T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_102308.2(CACNG6):​n.49+312T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 148,160 control chromosomes in the GnomAD database, including 2,740 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 0.19 (2740 hom., cov: 29)
• Consequence: CACNG6 NR_102308.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89
• Publications: 5 publications found

Genes affected

CACNG6 (HGNC:13625): (calcium voltage-gated channel auxiliary subunit gamma 6) 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 an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. 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). Alternative splicing results in multiple transcript variants. Variants in this gene have been associated with aspirin-intolerant asthma. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG6	NR_102308.2	n.49+312T>C		intron_variant	Intron 1 of 2
CACNG6	NM_145814.2	c.-1369T>C		upstream_gene_variant		ENST00000252729.7	NP_665813.1
CACNG6	NM_145815.2	c.-1369T>C		upstream_gene_variant			NP_665814.1
CACNG6	NM_031897.3	c.-1369T>C		upstream_gene_variant			NP_114103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.-1369T>C		upstream_gene_variant		1	NM_145814.2	ENSP00000252729.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 27814 AN: 148038 Hom.: 2742 Cov.: 29

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.188 AC: 27806 AN: 148160 Hom.: 2740 Cov.: 29 AF XY: 0.185 AC XY: 13361 AN XY: 72198

African (AFR) AF: 0.115 AC: 4680 AN: 40708

American (AMR) AF: 0.186 AC: 2794 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 815 AN: 3426

East Asian (EAS) AF: 0.224 AC: 1068 AN: 4774

South Asian (SAS) AF: 0.196 AC: 894 AN: 4568

European-Finnish (FIN) AF: 0.197 AC: 1917 AN: 9752

Middle Eastern (MID) AF: 0.139 AC: 40 AN: 288

European-Non Finnish (NFE) AF: 0.225 AC: 15009 AN: 66654

Other (OTH) AF: 0.181 AC: 375 AN: 2074

Alfa AF: 0.212 Hom.: 6990

Bravo AF: 0.184

Asia WGS AF: 0.173 AC: 603 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.89
PhyloP100		2.9
PromoterAI		-0.058	Neutral

Splicing

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

Other links and lift over

dbSNP: rs251850; hg19: chr19-54494763;