chr1-40642477-T-C

Position:

• chr1-40642477-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS3	NM_014747.3	c.-31-521A>G		intron_variant		ENST00000372684.8	NP_055562.2
RIMS3	XM_047435184.1	c.-31-521A>G		intron_variant			XP_047291140.1
RIMS3	XM_047435189.1	c.-31-521A>G		intron_variant			XP_047291145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS3	ENST00000372684.8	c.-31-521A>G		intron_variant		1	NM_014747.3	ENSP00000361769.3
RIMS3	ENST00000372683.1	c.-31-521A>G		intron_variant		1		ENSP00000361768.1

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

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.361

Alfa AF: 0.332 Hom.: 8068

Bravo AF: 0.381

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs11208590; hg19: chr1-41108149;