rs9341356

Positions:

• chr6-71911084-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014989.7(RIMS1):​c.164+23897G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 152,160 control chromosomes in the GnomAD database, including 482 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 0.067 (482 hom., cov: 32)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

RIMS1 (HGNC:17282): (regulating synaptic membrane exocytosis 1) The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.164+23897G>T		intron_variant		ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.164+23897G>T		intron_variant		1	NM_014989.7	ENSP00000428417	A2

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10240 AN: 152042 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0674 AC: 10248 AN: 152160 Hom.: 482 Cov.: 32 AF XY: 0.0673 AC XY: 5006 AN XY: 74378

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0579 Hom.: 461

Bravo AF: 0.0772

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.3
DANN	Benign	0.74

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: rs9341356; hg19: chr6-72620787;