rs10420331

Positions:

• chr19-53965814-G-A
• chr19-53965814-G-C

Variant summary

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

The ENST00000270458.4(CACNG8):​c.283+2389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,064 control chromosomes in the GnomAD database, including 17,860 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 0.48 (17860 hom., cov: 29)
• Consequence: CACNG8 ENST00000270458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

Genes affected

CACNG8 (HGNC:13628): (calcium voltage-gated channel auxiliary subunit gamma 8) 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. The mRNA for this gene is believed to initiate translation from a non-AUG (CUG) start codon. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG8	NM_031895.6	c.283+2389G>A		intron_variant		ENST00000270458.4	NP_114101.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG8	ENST00000270458.4	c.283+2389G>A		intron_variant		1	NM_031895.6	ENSP00000270458	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72320 AN: 150946 Hom.: 17846 Cov.: 29

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.479 AC: 72377 AN: 151064 Hom.: 17860 Cov.: 29 AF XY: 0.477 AC XY: 35160 AN XY: 73728

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.508

Alfa AF: 0.446 Hom.: 22989

Bravo AF: 0.491

Asia WGS AF: 0.555 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.82

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: rs10420331; hg19: chr19-54469068;