rs114505309

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014989.7(RIMS1):c.1209G>A(p.Ala403Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,445,990 control chromosomes in the GnomAD database, including 91,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6872 hom., cov: 32)

Exomes 𝑓: 0.36 ( 85013 hom. )

Consequence

RIMS1
NM_014989.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.39

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-72182680-G-A is Benign according to our data. Variant chr6-72182680-G-A is described in ClinVar as Benign. ClinVar VariationId is 95656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS1	NM_014989.7 link	c.1209G>A	p.Ala403Ala	synonymous_variant	Exon 6 of 34	ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6 link	c.1209G>A	p.Ala403Ala	synonymous_variant	Exon 6 of 34	1	NM_014989.7	ENSP00000428417.1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42418

AN:

151314

Hom.:

6879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.292

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.455

AC:

26400

AN:

57980

AF XY:

0.450

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.487

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.483

Gnomad OTH exome

AF:

0.455

GnomAD4 exome

AF:

0.358

AC:

463780

AN:

1294568

Hom.:

85013

Cov.:

AF XY:

0.358

AC XY:

226865

AN XY:

634486

show subpopulations

African (AFR)

AF:

0.118

AC:

2960

AN:

25046

American (AMR)

AF:

0.397

AC:

8080

AN:

20350

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

6854

AN:

19500

East Asian (EAS)

AF:

0.135

AC:

4057

AN:

30064

South Asian (SAS)

AF:

0.317

AC:

19490

AN:

61444

European-Finnish (FIN)

AF:

0.392

AC:

16413

AN:

41910

Middle Eastern (MID)

AF:

0.291

AC:

1146

AN:

3940

European-Non Finnish (NFE)

AF:

0.372

AC:

386852

AN:

1039090

Other (OTH)

AF:

0.337

AC:

17928

AN:

53224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

15363

30726

46089

61452

76815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12470

24940

37410

49880

62350

<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:

0.280

AC:

42413

AN:

151422

Hom.:

6872

Cov.:

AF XY:

0.282

AC XY:

20850

AN XY:

73990

show subpopulations

African (AFR)

AF:

0.117

AC:

4865

AN:

41424

American (AMR)

AF:

0.307

AC:

4671

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1136

AN:

3466

East Asian (EAS)

AF:

0.159

AC:

814

AN:

5130

South Asian (SAS)

AF:

0.286

AC:

1377

AN:

4820

European-Finnish (FIN)

AF:

0.374

AC:

3861

AN:

10332

Middle Eastern (MID)

AF:

0.272

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.365

AC:

24705

AN:

67734

Other (OTH)

AF:

0.285

AC:

599

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1524

3048

4571

6095

7619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.324

Hom.:

1146

Bravo

AF:

0.266

Asia WGS

AF:

0.201

AC:

695

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 31, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone-rod dystrophy 7

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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:2

Apr 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.4

PromoterAI

-0.055

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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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