8-103561561-C-A

Variant names:

• chr8-103561561-C-A
• rs75686122
• NM_001348484.3:c.176+60499C>A

Variant summary

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

The NM_001348484.3(RIMS2):​c.176+60499C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 152,116 control chromosomes in the GnomAD database, including 403 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 0.065 (403 hom., cov: 32)
• Consequence: RIMS2 NM_001348484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS2	NM_001348484.3	c.176+60499C>A		intron_variant	Intron 1 of 29	ENST00000696799.1	NP_001335413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS2	ENST00000696799.1	c.176+60499C>A		intron_variant	Intron 1 of 29		NM_001348484.3	ENSP00000512879.1

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9953 AN: 151998 Hom.: 404 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0654 AC: 9954 AN: 152116 Hom.: 403 Cov.: 32 AF XY: 0.0675 AC XY: 5015 AN XY: 74348

African (AFR) AF: 0.0269 AC: 1117 AN: 41518

American (AMR) AF: 0.0573 AC: 875 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3468

East Asian (EAS) AF: 0.0492 AC: 255 AN: 5182

South Asian (SAS) AF: 0.0881 AC: 424 AN: 4814

European-Finnish (FIN) AF: 0.101 AC: 1065 AN: 10570

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5860 AN: 67974

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0398 Hom.: 38

Bravo AF: 0.0581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.18
PhyloP100		-1.9
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: rs75686122; hg19: chr8-104573789;