rs2048137

Variant names:

• chr17-66871338-T-G
• rs2048137
• NM_145811.3:c.-103-5892T>G

Variant summary

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

The NM_145811.3(CACNG5):​c.-103-5892T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,864 control chromosomes in the GnomAD database, including 20,431 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 0.51 (20431 hom., cov: 31)
• Consequence: CACNG5 NM_145811.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 2 publications found

Genes affected

CACNG5 (HGNC:1409): (calcium voltage-gated channel auxiliary subunit gamma 5) The protein encoded by this gene is a type II transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. 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, a type I TARP and a calcium channel gamma subunit. This gene is a susceptibility locus for schizophrenia and bipolar disorder. [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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG5	NM_145811.3	c.-103-5892T>G		intron_variant	Intron 1 of 5	ENST00000533854.6	NP_665810.1
CACNG5	NM_001371476.1	c.-103-5892T>G		intron_variant	Intron 1 of 4		NP_001358405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG5	ENST00000533854.6	c.-103-5892T>G		intron_variant	Intron 1 of 5	2	NM_145811.3	ENSP00000436836.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77550 AN: 151746 Hom.: 20400 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.511 AC: 77642 AN: 151864 Hom.: 20431 Cov.: 31 AF XY: 0.508 AC XY: 37694 AN XY: 74228

African (AFR) AF: 0.554 AC: 22936 AN: 41412

American (AMR) AF: 0.421 AC: 6426 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1541 AN: 3466

East Asian (EAS) AF: 0.172 AC: 884 AN: 5150

South Asian (SAS) AF: 0.637 AC: 3063 AN: 4812

European-Finnish (FIN) AF: 0.469 AC: 4951 AN: 10556

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36185 AN: 67902

Other (OTH) AF: 0.494 AC: 1040 AN: 2106

Alfa AF: 0.519 Hom.: 7708

Bravo AF: 0.502

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.84
PhyloP100		-0.35
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: rs2048137; hg19: chr17-64867456;