Variant 8-103766524-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001348484.3(RIMS2):c.817A>G(p.Ile273Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,610,886 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 13 hom. )

Consequence

RIMS2
NM_001348484.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.833

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]

RIMS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003248334).

BP6

Variant 8-103766524-A-G is Benign according to our data. Variant chr8-103766524-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 730455.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00215 (327/152362) while in subpopulation NFE AF= 0.00385 (262/68032). AF 95% confidence interval is 0.00347. There are 1 homozygotes in gnomad4. There are 146 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS2	NM_001348484.3 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	6/30	ENST00000696799.1	NP_001335413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS2	ENST00000696799.1 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant	6/30		NM_001348484.3	ENSP00000512879	A1

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00385

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00227

AC:

560

AN:

246986

Hom.:

AF XY:

0.00229

AC XY:

307

AN XY:

133968

show subpopulations

Gnomad AFR exome

AF:

0.000389

Gnomad AMR exome

AF:

0.000996

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.00402

AC:

5868

AN:

1458524

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

2746

AN XY:

725530

show subpopulations

Gnomad4 AFR exome

AF:

0.000599

Gnomad4 AMR exome

AF:

0.000966

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.00496

Gnomad4 OTH exome

AF:

0.00322

GnomAD4 genome

AF:

0.00215

AC:

327

AN:

152362

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00385

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00213

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000520

AC:

ESP6500EA

AF:

0.00398

AC:

ExAC

AF:

0.00226

AC:

273

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.92

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.12

N;.

REVEL

Benign

0.030

Sift

Benign

1.0

T;.

Sift4G

Benign

0.36

T;T

Vest4

0.14

MVP

0.20

ClinPred

0.0045

GERP RS

1.4

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over