rs484596

Positions:

• chr6-72047095-C-A
• chr6-72047095-C-G

Variant summary

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

The NM_014989.7(RIMS1):​c.246-49854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,944 control chromosomes in the GnomAD database, including 15,453 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 0.45 (15453 hom., cov: 32)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.246-49854C>A		intron_variant		ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.246-49854C>A		intron_variant		1	NM_014989.7	ENSP00000428417	A2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67649 AN: 151824 Hom.: 15437 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.446 AC: 67710 AN: 151944 Hom.: 15453 Cov.: 32 AF XY: 0.446 AC XY: 33151 AN XY: 74270

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.444

Alfa AF: 0.397 Hom.: 2446

Bravo AF: 0.457

Asia WGS AF: 0.534 AC: 1851 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.42

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: rs484596; hg19: chr6-72756798;