11-8128206-T-G

Variant summary

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

The NM_001206671.4(RIC3):c.522-1399A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 457,318 control chromosomes in the GnomAD database, including 1,891 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 0.089 (719 hom., cov: 32)
  • Exomes 𝑓: 0.080 (1172 hom.)
• Consequence: RIC3 NM_001206671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

Genes affected

RIC3 (HGNC:30338): (RIC3 acetylcholine receptor chaperone) This gene encodes a member of the resistance to inhibitors of cholinesterase 3-like family which functions as a chaperone of specific 5-hydroxytryptamine type 3 receptor and nicotinic acetylcholine receptor subtypes. The encoded protein influences the folding and assembly of these receptor subunits in the endoplasmic reticulum and expression on the cell surface. This protein contains an N-terminal transmembrane domain, a proline-rich spacer, and a cytosolic C-terminal coiled-coil domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIC3	NM_001206671.4	c.522-1399A>C		intron_variant		ENST00000309737.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIC3	ENST00000309737.11	c.522-1399A>C		intron_variant		1	NM_001206671.4	A1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13495 AN: 152146 Hom.: 717 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0814

GnomAD3 exomes AF: 0.0857 AC: 11948 AN: 139350 Hom.: 630 AF XY: 0.0851 AC XY: 6400 AN XY: 75236

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.0975

Gnomad EAS exome AF: 0.0501

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.0605

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0696

GnomAD4 exome AF: 0.0803 AC: 24492 AN: 305054 Hom.: 1172 Cov.: 0 AF XY: 0.0813 AC XY: 14122 AN XY: 173636

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.0981

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0587

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0688

GnomAD4 genome AF: 0.0887 AC: 13505 AN: 152264 Hom.: 719 Cov.: 32 AF XY: 0.0892 AC XY: 6642 AN XY: 74448

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0888

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0801

Alfa AF: 0.0663 Hom.: 505

Bravo AF: 0.0926

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.9
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1528133; hg19: chr11-8149753; COSMIC: COSV58302424;