NM_014989.7:c.1776G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_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. 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

Publications

10 publications found

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 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

RIMS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

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.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2620 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6 link	c.1776G>A	p.Glu592Glu	synonymous_variant	Exon 8 of 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

GnomAD2 exomes

AF:

0.0129

AC:

3163

AN:

245860

AF XY:

0.0123

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 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

African (AFR)

AF:

0.0234

AC:

782

AN:

33378

American (AMR)

AF:

0.00522

AC:

232

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.00933

AC:

243

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.00567

AC:

486

AN:

85658

European-Finnish (FIN)

AF:

0.0161

AC:

860

AN:

53300

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0166

AC:

18460

AN:

1110196

Other (OTH)

AF:

0.0134

AC:

805

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

925

1851

2776

3702

4627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

662

1324

1986

2648

3310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0172

AC:

2620

AN:

152100

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1252

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0237

AC:

984

AN:

41504

American (AMR)

AF:

0.0122

AC:

186

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00951

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00540

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10600

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0172

AC:

1172

AN:

67960

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

133

267

400

534

667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0152

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

Jan 01, 2012

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

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone-rod dystrophy 7

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.4

(source)

DANN

Benign

0.50

PhyloP100

1.2

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over