rs77121218

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_014989.7(RIMS1):c.1776G>A(p.Glu592Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,610,726 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 25 hom., cov: 32)

Exomes 𝑓: 0.015 ( 192 hom. )

Consequence

RIMS1
NM_014989.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: 1.22

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 6-72235647-G-A is Benign according to our data. Variant chr6-72235647-G-A is described in ClinVar as [Benign]. Clinvar id is 260494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-72235647-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0172 (2620/152100) while in subpopulation AFR AF= 0.0237 (984/41504). AF 95% confidence interval is 0.0225. There are 25 homozygotes in gnomad4. There are 1252 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2620 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS1	NM_014989.7 link	c.1776G>A	p.Glu592Glu	synonymous_variant	8/34	ENST00000521978.6	NP_055804.2	Q86UR5-1Q3ZCW0B7Z7W2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6 link	c.1776G>A	p.Glu592Glu	synonymous_variant	8/34	1	NM_014989.7	ENSP00000428417.1		Q86UR5-1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2622

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0129

AC:

3163

AN:

245860

Hom.:

AF XY:

0.0123

AC XY:

1636

AN XY:

133258

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00522

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00601

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.0150

AC:

21882

AN:

1458626

Hom.:

192

Cov.:

AF XY:

0.0148

AC XY:

10723

AN XY:

725400

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.00522

Gnomad4 ASJ exome

AF:

0.00933

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00567

Gnomad4 FIN exome

AF:

0.0161

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0172

AC:

2620

AN:

152100

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1252

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.0163

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2012

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cone-rod dystrophy 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.4

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over