chr8-103541180-A-C

Variant names:

• chr8-103541180-A-C
• rs2080610
• NM_001348484.3:c.176+40118A>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.176+40118A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,982 control chromosomes in the GnomAD database, including 11,073 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 0.38 (11073 hom., cov: 32)
• Consequence: RIMS2 NM_001348484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS2	NM_001348484.3	MANE Select	c.176+40118A>C		intron	N/A	NP_001335413.1
	RIMS2	NM_001395654.1		c.176+40118A>C		intron	N/A	NP_001382583.1
	RIMS2	NM_001395652.1		c.176+40118A>C		intron	N/A	NP_001382581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS2	ENST00000696799.1	MANE Select	c.176+40118A>C		intron	N/A	ENSP00000512879.1
	RIMS2	ENST00000666250.1		c.176+40118A>C		intron	N/A	ENSP00000499454.1
	RIMS2	ENST00000705945.1		c.176+40118A>C		intron	N/A	ENSP00000516182.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57069 AN: 151864 Hom.: 11060 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.376 AC: 57119 AN: 151982 Hom.: 11073 Cov.: 32 AF XY: 0.374 AC XY: 27764 AN XY: 74272

African (AFR) AF: 0.401 AC: 16596 AN: 41432

American (AMR) AF: 0.298 AC: 4549 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1316 AN: 3464

East Asian (EAS) AF: 0.111 AC: 573 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4822

European-Finnish (FIN) AF: 0.473 AC: 4984 AN: 10544

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26580 AN: 67954

Other (OTH) AF: 0.349 AC: 738 AN: 2114

Alfa AF: 0.379 Hom.: 5856

Bravo AF: 0.361

Asia WGS AF: 0.227 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.55
PhyloP100		-2.1
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: rs2080610; hg19: chr8-104553408;