8-103620147-C-T

Variant names:

• chr8-103620147-C-T
• rs10505047
• NM_001348484.3:c.177-32058C>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.177-32058C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,970 control chromosomes in the GnomAD database, including 3,037 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 0.19 (3037 hom., cov: 32)
• Consequence: RIMS2 NM_001348484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS2	NM_001348484.3	c.177-32058C>T		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.177-32058C>T		intron_variant	Intron 1 of 29		NM_001348484.3	ENSP00000512879.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29378 AN: 151852 Hom.: 3034 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.193 AC: 29395 AN: 151970 Hom.: 3037 Cov.: 32 AF XY: 0.195 AC XY: 14505 AN XY: 74264

African (AFR) AF: 0.143 AC: 5930 AN: 41464

American (AMR) AF: 0.191 AC: 2915 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3466

East Asian (EAS) AF: 0.110 AC: 567 AN: 5156

South Asian (SAS) AF: 0.201 AC: 968 AN: 4822

European-Finnish (FIN) AF: 0.244 AC: 2577 AN: 10546

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14905 AN: 67930

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.213 Hom.: 440

Bravo AF: 0.184

Asia WGS AF: 0.171 AC: 594 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.2
DANN	Benign	0.40
PhyloP100		1.4
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: rs10505047; hg19: chr8-104632375;