chr11-8162601-G-A

Variant names:

• chr11-8162601-G-A
• rs16936464
• NM_001206671.4:c.124+6265C>T

Variant summary

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

The NM_001206671.4(RIC3):​c.124+6265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 147,414 control chromosomes in the GnomAD database, including 573 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 0.081 (573 hom., cov: 29)
• Consequence: RIC3 NM_001206671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 1 publications found

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]

RIC3 Gene-Disease associations (from GenCC):

• Parkinson disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• movement disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC3	NM_001206671.4	MANE Select	c.124+6265C>T		intron	N/A	NP_001193600.1
	RIC3	NM_024557.6		c.124+6265C>T		intron	N/A	NP_078833.3
	RIC3	NM_001346693.2		c.-73+6265C>T		intron	N/A	NP_001333622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC3	ENST00000309737.11	TSL:1 MANE Select	c.124+6265C>T		intron	N/A	ENSP00000308820.6
	RIC3	ENST00000343202.8	TSL:1	c.124+6265C>T		intron	N/A	ENSP00000344904.4
	RIC3	ENST00000425599.6	TSL:1	c.124+6265C>T		intron	N/A	ENSP00000395320.2

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 11889 AN: 147348 Hom.: 571 Cov.: 29

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0597

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0265

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0734

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

GnomAD4 genome AF: 0.0808 AC: 11904 AN: 147414 Hom.: 573 Cov.: 29 AF XY: 0.0815 AC XY: 5834 AN XY: 71624

African (AFR) AF: 0.117 AC: 4677 AN: 39906

American (AMR) AF: 0.0793 AC: 1179 AN: 14860

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 252 AN: 3438

East Asian (EAS) AF: 0.0547 AC: 270 AN: 4934

South Asian (SAS) AF: 0.112 AC: 514 AN: 4608

European-Finnish (FIN) AF: 0.0720 AC: 669 AN: 9294

Middle Eastern (MID) AF: 0.0216 AC: 6 AN: 278

European-Non Finnish (NFE) AF: 0.0616 AC: 4136 AN: 67160

Other (OTH) AF: 0.0723 AC: 147 AN: 2032

Alfa AF: 0.0665 Hom.: 200

Bravo AF: 0.0823

Asia WGS AF: 0.0900 AC: 314 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.61
PhyloP100		-0.40
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: rs16936464; hg19: chr11-8184148;