rs1156813

Variant names:

• chr8-104234890-C-T
• rs1156813
• NM_001348484.3:c.4109-10026C>T

Variant summary

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

The NM_001348484.3(RIMS2):​c.4109-10026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,076 control chromosomes in the GnomAD database, including 2,468 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 0.16 (2468 hom., cov: 32)
• Consequence: RIMS2 NM_001348484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 4 publications found

Genes affected

RIMS2 (HGNC:17283): (regulating synaptic membrane exocytosis 2) The protein encoded by this gene is a presynaptic protein that interacts with RAB3, a protein important for normal neurotransmitter release. The encoded protein can also bind several other synaptic proteins, including UNC-13 homolog B, ELKS/Rab6-interacting/CAST family member 1, and synaptotagmin 1. This protein is involved in synaptic membrane exocytosis. Polymorphisms in this gene have been associated with degenerative lumbar scoliosis. [provided by RefSeq, Feb 2017]

RIMS2 Gene-Disease associations (from GenCC):

• cone-rod synaptic disorder syndrome, congenital nonprogressive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• cone-rod synaptic disorder, congenital nonprogressive

  Inheritance: AR Classification: STRONG Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -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 = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS2	NM_001348484.3	c.4109-10026C>T		intron_variant	Intron 25 of 29	ENST00000696799.1	NP_001335413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS2	ENST00000696799.1	c.4109-10026C>T		intron_variant	Intron 25 of 29		NM_001348484.3	ENSP00000512879.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24155 AN: 151958 Hom.: 2468 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.159 AC: 24159 AN: 152076 Hom.: 2468 Cov.: 32 AF XY: 0.155 AC XY: 11561 AN XY: 74348

African (AFR) AF: 0.0509 AC: 2114 AN: 41542

American (AMR) AF: 0.130 AC: 1987 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0918 AC: 442 AN: 4814

European-Finnish (FIN) AF: 0.242 AC: 2560 AN: 10566

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15805 AN: 67916

Other (OTH) AF: 0.162 AC: 342 AN: 2108

Alfa AF: 0.191 Hom.: 377

Bravo AF: 0.147

Asia WGS AF: 0.0450 AC: 158 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	1.6
DANN	Benign	0.77
PhyloP100		-0.27
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: rs1156813; hg19: chr8-105247118;