1-40642477-T-C

Variant names:

• chr1-40642477-T-C
• rs11208590
• NM_014747.3:c.-31-521A>G

Variant summary

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

The NM_014747.3(RIMS3):​c.-31-521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,804 control chromosomes in the GnomAD database, including 11,425 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 0.37 (11425 hom., cov: 31)
• Consequence: RIMS3 NM_014747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 6 publications found

Genes affected

RIMS3 (HGNC:21292): (regulating synaptic membrane exocytosis 3) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in several processes, including calcium ion-regulated exocytosis of neurotransmitter; modulation of chemical synaptic transmission; and regulation of synapse organization. Predicted to be located in presynaptic active zone. Predicted to be part of glutamatergic synapse. Predicted to be active in cytoskeleton of presynaptic active zone; postsynaptic cytosol; and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014747.3. 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
	RIMS3	NM_014747.3	MANE Select	c.-31-521A>G		intron	N/A	NP_055562.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS3	ENST00000372684.8	TSL:1 MANE Select	c.-31-521A>G		intron	N/A	ENSP00000361769.3	Q9UJD0-1
	RIMS3	ENST00000372683.1	TSL:1	c.-31-521A>G		intron	N/A	ENSP00000361768.1	Q9UJD0-1
	RIMS3	ENST00000858245.1		c.-31-521A>G		intron	N/A	ENSP00000528304.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56521 AN: 151684 Hom.: 11396 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.373 AC: 56593 AN: 151804 Hom.: 11425 Cov.: 31 AF XY: 0.369 AC XY: 27356 AN XY: 74194

African (AFR) AF: 0.537 AC: 22212 AN: 41364

American (AMR) AF: 0.322 AC: 4914 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1015 AN: 5158

South Asian (SAS) AF: 0.275 AC: 1321 AN: 4796

European-Finnish (FIN) AF: 0.302 AC: 3192 AN: 10562

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21932 AN: 67886

Other (OTH) AF: 0.361 AC: 759 AN: 2104

Alfa AF: 0.342 Hom.: 11367

Bravo AF: 0.381

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.69
PhyloP100		-1.0
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: rs11208590; hg19: chr1-41108149;