chr8-104220555-A-G

Variant names:

• chr8-104220555-A-G
• rs2511571
• NM_001348484.3:c.4109-24361A>G

Variant summary

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

The NM_001348484.3(RIMS2):​c.4109-24361A>G 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 152,118 control chromosomes in the GnomAD database, including 2,469 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 (2469 hom., cov: 32)
• Consequence: RIMS2 NM_001348484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348484.3. 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
	RIMS2	NM_001348484.3	MANE Select	c.4109-24361A>G		intron	N/A	NP_001335413.1
	RIMS2	NM_001395654.1		c.3968-24361A>G		intron	N/A	NP_001382583.1
	RIMS2	NM_001395652.1		c.3962-24361A>G		intron	N/A	NP_001382581.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS2	ENST00000696799.1	MANE Select	c.4109-24361A>G		intron	N/A	ENSP00000512879.1
	RIMS2	ENST00000408894.7	TSL:1	c.3356-24361A>G		intron	N/A	ENSP00000386228.3
	RIMS2	ENST00000262231.14	TSL:1	c.2852-24361A>G		intron	N/A	ENSP00000262231.10

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24150 AN: 152000 Hom.: 2469 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.159 AC: 24154 AN: 152118 Hom.: 2469 Cov.: 32 AF XY: 0.155 AC XY: 11544 AN XY: 74370

African (AFR) AF: 0.0511 AC: 2121 AN: 41532

American (AMR) AF: 0.129 AC: 1975 AN: 15270

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

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0919 AC: 442 AN: 4810

European-Finnish (FIN) AF: 0.240 AC: 2535 AN: 10568

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15828 AN: 67976

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.208 Hom.: 1860

Bravo AF: 0.147

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.22
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: rs2511571; hg19: chr8-105232783;