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GeneBe

8-103885391-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001348484.3(RIMS2):c.924C>T(p.Thr308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,612,482 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 19 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

RIMS2
NM_001348484.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29
Variant links:
Genes affected
RIMS2 (HGNC:17283): (regulating synaptic membrane exocytosis 2) The protein encoded by this gene is a presynaptic protein that interacts with RAB3, a protein important for normal neurotransmitter release. The encoded protein can also bind several other synaptic proteins, including UNC-13 homolog B, ELKS/Rab6-interacting/CAST family member 1, and synaptotagmin 1. This protein is involved in synaptic membrane exocytosis. Polymorphisms in this gene have been associated with degenerative lumbar scoliosis. [provided by RefSeq, Feb 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-103885391-C-T is Benign according to our data. Variant chr8-103885391-C-T is described in ClinVar as [Benign]. Clinvar id is 780777.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.29 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00866 (1315/151926) while in subpopulation AFR AF= 0.0295 (1224/41488). AF 95% confidence interval is 0.0281. There are 19 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RIMS2NM_001348484.3 linkuse as main transcriptc.924C>T p.Thr308= synonymous_variant 7/30 ENST00000696799.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RIMS2ENST00000696799.1 linkuse as main transcriptc.924C>T p.Thr308= synonymous_variant 7/30 NM_001348484.3 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00865
AC:
1313
AN:
151808
Hom.:
19
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0295
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00296
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00292
Gnomad SAS
AF:
0.000623
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00911
GnomAD3 exomes
AF:
0.00249
AC:
617
AN:
248028
Hom.:
11
AF XY:
0.00193
AC XY:
260
AN XY:
134538
show subpopulations
Gnomad AFR exome
AF:
0.0324
Gnomad AMR exome
AF:
0.00105
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00257
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000169
Gnomad OTH exome
AF:
0.00150
GnomAD4 exome
AF:
0.00120
AC:
1749
AN:
1460556
Hom.:
24
Cov.:
31
AF XY:
0.00111
AC XY:
806
AN XY:
726606
show subpopulations
Gnomad4 AFR exome
AF:
0.0343
Gnomad4 AMR exome
AF:
0.00119
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00595
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000138
Gnomad4 OTH exome
AF:
0.00227
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00866
AC:
1315
AN:
151926
Hom.:
19
Cov.:
32
AF XY:
0.00846
AC XY:
628
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.0295
Gnomad4 AMR
AF:
0.00296
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00292
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00901
Alfa
AF:
0.00374
Hom.:
5
Bravo
AF:
0.0100
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
11
Dann
Benign
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34681663; hg19: chr8-104897619; COSMIC: COSV51664224; API