chr6-72258249-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_014989.7(RIMS1):c.2895G>A(p.Pro965Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,340 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 120 hom. )

Consequence

RIMS1
NM_014989.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.253

Publications

2 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.139).

BP6

Variant 6-72258249-G-A is Benign according to our data. Variant chr6-72258249-G-A is described in ClinVar as Benign. ClinVar VariationId is 260495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.253 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0111 (16278/1461068) while in subpopulation MID AF = 0.0207 (119/5760). AF 95% confidence interval is 0.0176. There are 120 homozygotes in GnomAdExome4. There are 8121 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1252 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS1	NM_014989.7 link	c.2895G>A	p.Pro965Pro	synonymous_variant	Exon 17 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.2895G>A	p.Pro965Pro	synonymous_variant	Exon 17 of 34	1	NM_014989.7	ENSP00000428417.1		Q86UR5-1

Frequencies

GnomAD3 genomes

AF:

0.00822

AC:

1251

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00446

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00909

GnomAD2 exomes

AF:

0.00876

AC:

2175

AN:

248356

AF XY:

0.00880

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00433

Gnomad ASJ exome

AF:

0.00836

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0111

AC:

16278

AN:

1461068

Hom.:

120

Cov.:

AF XY:

0.0112

AC XY:

8121

AN XY:

726816

show subpopulations

African (AFR)

AF:

0.00179

AC:

AN:

33446

American (AMR)

AF:

0.00457

AC:

204

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00896

AC:

234

AN:

26114

East Asian (EAS)

AF:

0.000605

AC:

AN:

39666

South Asian (SAS)

AF:

0.00758

AC:

654

AN:

86236

European-Finnish (FIN)

AF:

0.0120

AC:

639

AN:

53342

Middle Eastern (MID)

AF:

0.0207

AC:

119

AN:

5760

European-Non Finnish (NFE)

AF:

0.0123

AC:

13714

AN:

1111504

Other (OTH)

AF:

0.0104

AC:

630

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

759

1519

2278

3038

3797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.00822

AC:

1252

AN:

152272

Hom.:

Cov.:

AF XY:

0.00801

AC XY:

596

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41584

American (AMR)

AF:

0.00446

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.00767

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0116

AC:

123

AN:

10610

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0128

AC:

874

AN:

68020

Other (OTH)

AF:

0.00900

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0103

Hom.:

Bravo

AF:

0.00751

Asia WGS

AF:

0.00260

AC:

AN:

3476

EpiCase

AF:

0.0136

EpiControl

AF:

0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RIMS1: BP4, BP7, BS1, BS2 -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.25

Mutation Taster

=295/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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