rs502046

Variant names:

• chr6-71998178-T-C
• rs502046
• NM_014989.7:c.245+29115T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-71998178-T-C
• chr6-71998178-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

RIMS1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 7

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.245+29115T>C		intron_variant	Intron 2 of 33	ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.245+29115T>C		intron_variant	Intron 2 of 33	1	NM_014989.7	ENSP00000428417.1

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

African (AFR) AF: 0.299 AC: 12387 AN: 41462

American (AMR) AF: 0.478 AC: 7301 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1820 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1758 AN: 5148

South Asian (SAS) AF: 0.509 AC: 2444 AN: 4802

European-Finnish (FIN) AF: 0.549 AC: 5790 AN: 10556

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34818 AN: 67952

Other (OTH) AF: 0.437 AC: 923 AN: 2112

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
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs502046; hg19: chr6-72707881;