8-104222586-T-C

Variant names:

• chr8-104222586-T-C
• rs2511576
• NM_001348484.3:c.4109-22330T>C

Variant summary

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

The NM_001348484.3(RIMS2):​c.4109-22330T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,024 control chromosomes in the GnomAD database, including 8,679 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 0.33 (8679 hom., cov: 32)
• Consequence: RIMS2 NM_001348484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 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.4109-22330T>C		intron	N/A	NP_001335413.1
	RIMS2	NM_001395654.1		c.3968-22330T>C		intron	N/A	NP_001382583.1
	RIMS2	NM_001395652.1		c.3962-22330T>C		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.4109-22330T>C		intron	N/A	ENSP00000512879.1
	RIMS2	ENST00000408894.7	TSL:1	c.3356-22330T>C		intron	N/A	ENSP00000386228.3
	RIMS2	ENST00000262231.14	TSL:1	c.2852-22330T>C		intron	N/A	ENSP00000262231.10

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50461 AN: 151906 Hom.: 8661 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.332 AC: 50532 AN: 152024 Hom.: 8679 Cov.: 32 AF XY: 0.326 AC XY: 24205 AN XY: 74320

African (AFR) AF: 0.423 AC: 17541 AN: 41436

American (AMR) AF: 0.291 AC: 4449 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1104 AN: 5162

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2836 AN: 10586

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21209 AN: 67968

Other (OTH) AF: 0.324 AC: 685 AN: 2114

Alfa AF: 0.321 Hom.: 1006

Bravo AF: 0.337

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.7
DANN	Benign	0.66
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: rs2511576; hg19: chr8-105234814;