Variant 8-103885459-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001348484.3(RIMS2):c.992A>T(p.Asp331Val) variant causes a missense change. The variant allele was found at a frequency of 0.000406 in 1,612,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

RIMS2
NM_001348484.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004315287).

BP6

Variant 8-103885459-A-T is Benign according to our data. Variant chr8-103885459-A-T is described in ClinVar as [Benign]. Clinvar id is 716390.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00225 (342/151988) while in subpopulation AFR AF= 0.00791 (328/41492). AF 95% confidence interval is 0.0072. There are 0 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS2	NM_001348484.3 linkuse as main transcript	c.992A>T	p.Asp331Val	missense_variant	7/30	ENST00000696799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS2	ENST00000696799.1 linkuse as main transcript	c.992A>T	p.Asp331Val	missense_variant	7/30		NM_001348484.3	A1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

341

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00790

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000451

AC:

112

AN:

248372

Hom.:

AF XY:

0.000408

AC XY:

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.00653

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000214

AC:

312

AN:

1460660

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.00752

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

151988

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

164

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00791

Gnomad4 AMR

AF:

0.000591

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.00237

ESP6500AA

AF:

0.00717

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000621

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.070

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.0043

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.5

N;.;D;D;D;D;N

REVEL

Benign

0.16

Sift

Benign

0.062

T;.;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T;T

Polyphen

0.083, 0.12, 0.16

.;.;.;B;B;.;B

Vest4

0.37

MVP

0.32

ClinPred

0.038

GERP RS

4.1

gMVP

0.38

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