Genetic Variant RIMS1:c.-302C>T (chr6-71886722-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014989.7(RIMS1):c.-302C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00096 in 185,472 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

RIMS1
NM_014989.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.345

Publications

1 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, Illumina, Ambry Genetics, 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-71886722-C-T is Benign according to our data. Variant chr6-71886722-C-T is described in ClinVar as Benign. ClinVar VariationId is 357821.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 134 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014989.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RIMS1	NM_014989.7	MANE Select	c.-302C>T	5_prime_UTR	Exon 1 of 34	NP_055804.2
RIMS1	NM_001350413.1		c.-302C>T	5_prime_UTR	Exon 1 of 4	NP_001337342.1
RIMS1	NM_001350411.1		c.-302C>T	5_prime_UTR	Exon 1 of 4	NP_001337340.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.-302C>T	5_prime_UTR	Exon 1 of 34	ENSP00000428417.1	Q86UR5-1
RIMS1	ENST00000697193.1		c.-302C>T	5_prime_UTR	Exon 1 of 29	ENSP00000513179.1	A0A8V8TKU9
RIMS1	ENST00000491071.6	TSL:5	c.-302C>T	5_prime_UTR	Exon 1 of 28	ENSP00000430101.1	Q86UR5-3

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

133

AN:

151048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00119

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000975

Gnomad OTH

AF:

0.00193

GnomAD4 exome

AF:

0.00128

AC:

AN:

34314

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

17548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1094

American (AMR)

AF:

0.00

AC:

AN:

874

Ashkenazi Jewish (ASJ)

AF:

0.00156

AC:

AN:

1282

East Asian (EAS)

AF:

0.00

AC:

AN:

2604

South Asian (SAS)

AF:

0.00836

AC:

AN:

1196

European-Finnish (FIN)

AF:

0.000373

AC:

AN:

2678

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.000952

AC:

AN:

22062

Other (OTH)

AF:

0.00343

AC:

AN:

2330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000886

AC:

134

AN:

151158

Hom.:

Cov.:

AF XY:

0.000826

AC XY:

AN XY:

73846

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41416

American (AMR)

AF:

0.00119

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.00704

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000976

AC:

AN:

67656

Other (OTH)

AF:

0.00191

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000793

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone-rod dystrophy 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.34

PromoterAI

-0.044

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over