rs740557

Positions:

• chr17-67024561-C-G
• chr17-67024561-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014405.4(CACNG4):​c.305-299C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,300 control chromosomes in the GnomAD database, including 865 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 0.090 (865 hom., cov: 33)
• Consequence: CACNG4 NM_014405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

Genes affected

CACNG4 (HGNC:1408): (calcium voltage-gated channel auxiliary subunit gamma 4) The protein encoded by this gene is a type I 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 II TARP and a calcium channel gamma subunit. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG4	NM_014405.4	c.305-299C>G		intron_variant		ENST00000262138.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG4	ENST00000262138.4	c.305-299C>G		intron_variant		1	NM_014405.4	P1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13690 AN: 152182 Hom.: 866 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0898 AC: 13684 AN: 152300 Hom.: 865 Cov.: 33 AF XY: 0.0878 AC XY: 6541 AN XY: 74486

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0603 Hom.: 69

Bravo AF: 0.0887

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs740557; hg19: chr17-65020677;