1-40635900-A-G

Position:

• chr1-40635900-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014747.3(RIMS3):​c.359+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,611,386 control chromosomes in the GnomAD database, including 484,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48431 hom., cov: 32)
  • Exomes 𝑓: 0.77 (436223 hom.)
• Consequence: RIMS3 NM_014747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.369

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-40635900-A-G is Benign according to our data. Variant chr1-40635900-A-G is described in ClinVar as [Benign]. Clinvar id is 1300631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS3	NM_014747.3	c.359+16T>C		intron_variant		ENST00000372684.8
RIMS3	XM_047435184.1	c.359+16T>C		intron_variant
RIMS3	XM_047435189.1	c.359+16T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8	c.359+16T>C		intron_variant		1	NM_014747.3	P1
RIMS3	ENST00000372683.1	c.359+16T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120492 AN: 152080 Hom.: 48389 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.784

GnomAD3 exomes AF: 0.734 AC: 182815 AN: 249006 Hom.: 68391 AF XY: 0.731 AC XY: 98555 AN XY: 134848

Gnomad AFR exome AF: 0.901

Gnomad AMR exome AF: 0.652

Gnomad ASJ exome AF: 0.725

Gnomad EAS exome AF: 0.562

Gnomad SAS exome AF: 0.590

Gnomad FIN exome AF: 0.773

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.748

GnomAD4 exome AF: 0.769 AC: 1122697 AN: 1459188 Hom.: 436223 Cov.: 55 AF XY: 0.764 AC XY: 554788 AN XY: 725954

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.769

Gnomad4 NFE exome AF: 0.794

Gnomad4 OTH exome AF: 0.756

GnomAD4 genome AF: 0.792 AC: 120583 AN: 152198 Hom.: 48431 Cov.: 32 AF XY: 0.785 AC XY: 58394 AN XY: 74426

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.776

Alfa AF: 0.791 Hom.: 8897

Bravo AF: 0.795

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.1
DANN	Benign	0.45

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: rs2253835; hg19: chr1-41101572;