19-53977896-T-C

Variant names:

• chr19-53977896-T-C
• rs11084307
• NM_031895.6:c.284-250T>C

Variant summary

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

The NM_031895.6(CACNG8):​c.284-250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,140 control chromosomes in the GnomAD database, including 6,788 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 0.27 (6788 hom., cov: 32)
• Consequence: CACNG8 NM_031895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG8	NM_031895.6	c.284-250T>C		intron_variant	Intron 1 of 3	ENST00000270458.4	NP_114101.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG8	ENST00000270458.4	c.284-250T>C		intron_variant	Intron 1 of 3	1	NM_031895.6	ENSP00000270458.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40938 AN: 152018 Hom.: 6779 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.269 AC: 40948 AN: 152140 Hom.: 6788 Cov.: 32 AF XY: 0.271 AC XY: 20146 AN XY: 74366

African (AFR) AF: 0.0796 AC: 3307 AN: 41550

American (AMR) AF: 0.313 AC: 4784 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3470

East Asian (EAS) AF: 0.494 AC: 2538 AN: 5142

South Asian (SAS) AF: 0.371 AC: 1787 AN: 4820

European-Finnish (FIN) AF: 0.265 AC: 2802 AN: 10582

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23167 AN: 67988

Other (OTH) AF: 0.313 AC: 661 AN: 2112

Alfa AF: 0.315 Hom.: 23970

Bravo AF: 0.264

Asia WGS AF: 0.430 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		1.9

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: rs11084307; hg19: chr19-54481150;