rs502046

chr6-71998178-T-Cchr6-71998178-T-G

Variant summary

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

The NM_014989.7(RIMS1):c.245+29115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,966 control chromosomes in the GnomAD database, including 15,746 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 (15746 hom., cov: 31)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS1	NM_014989.7	c.245+29115T>C		intron_variant		ENST00000521978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS1	ENST00000521978.6	c.245+29115T>C		intron_variant		1	NM_014989.7	A2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67652 AN: 151848 Hom.: 15744 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.445 AC: 67698 AN: 151966 Hom.: 15746 Cov.: 31 AF XY: 0.448 AC XY: 33290 AN XY: 74260

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.437

Alfa AF: 0.402 Hom.: 1790

Bravo AF: 0.433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.28
Dann	Benign	0.65

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: rs502046; hg19: chr6-72707881;