6-72392740-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014989.7(RIMS1):c.4548C>T(p.Phe1516Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,611,926 control chromosomes in the GnomAD database, including 43,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3362 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40117 hom. )

Consequence

RIMS1
NM_014989.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.35

Publications

13 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=0.027).

BP6

Variant 6-72392740-C-T is Benign according to our data. Variant chr6-72392740-C-T is described in ClinVar as Benign. ClinVar VariationId is 260498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS1	NM_014989.7 link	c.4548C>T	p.Phe1516Phe	synonymous_variant	Exon 31 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.4548C>T	p.Phe1516Phe	synonymous_variant	Exon 31 of 34	1	NM_014989.7	ENSP00000428417.1		Q86UR5-1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30524

AN:

151870

Hom.:

3360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.0177

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.209

AC:

52052

AN:

249168

AF XY:

0.220

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.228

AC:

332575

AN:

1459938

Hom.:

40117

Cov.:

AF XY:

0.231

AC XY:

167619

AN XY:

726374

show subpopulations

African (AFR)

AF:

0.153

AC:

5131

AN:

33454

American (AMR)

AF:

0.110

AC:

4905

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

7046

AN:

26118

East Asian (EAS)

AF:

0.0168

AC:

666

AN:

39678

South Asian (SAS)

AF:

0.297

AC:

25612

AN:

86186

European-Finnish (FIN)

AF:

0.257

AC:

13719

AN:

53390

Middle Eastern (MID)

AF:

0.270

AC:

1554

AN:

5764

European-Non Finnish (NFE)

AF:

0.235

AC:

260902

AN:

1110324

Other (OTH)

AF:

0.216

AC:

13040

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

11764

23527

35291

47054

58818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8812

17624

26436

35248

44060

<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:

0.201

AC:

30556

AN:

151988

Hom.:

3362

Cov.:

AF XY:

0.203

AC XY:

15080

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.158

AC:

6554

AN:

41438

American (AMR)

AF:

0.148

AC:

2261

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

934

AN:

3466

East Asian (EAS)

AF:

0.0177

AC:

AN:

5184

South Asian (SAS)

AF:

0.293

AC:

1410

AN:

4818

European-Finnish (FIN)

AF:

0.258

AC:

2719

AN:

10528

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15882

AN:

67980

Other (OTH)

AF:

0.209

AC:

441

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1255

2510

3764

5019

6274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.222

Hom.:

6532

Bravo

AF:

0.189

Asia WGS

AF:

0.153

AC:

535

AN:

3478

EpiCase

AF:

0.245

EpiControl

AF:

0.241

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

- -

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. -

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

-0.28

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

1.4

Mutation Taster

=78/22

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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