Variant chr12-130407728-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001393629.1(RIMBP2):c.3691G>A(p.Glu1231Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,612,764 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 7 hom. )

Consequence

RIMBP2
NM_001393629.1 missense, splice_region

Scores

Splicing: ADA: 0.7713

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74

Variant links:

Genes affected

RIMBP2 (HGNC:30339): (RIMS binding protein 2) Predicted to be involved in neuromuscular synaptic transmission. Predicted to be located in plasma membrane and synapse. Predicted to be active in presynaptic active zone cytoplasmic component. [provided by Alliance of Genome Resources, Apr 2022]

RIMBP2 links:

PIWIL1 (HGNC:):

PIWIL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06452593).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP2	NM_001393629.1 linkuse as main transcript	c.3691G>A	p.Glu1231Lys	missense_variant, splice_region_variant	20/23	ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1 linkuse as main transcript	c.3691G>A	p.Glu1231Lys	missense_variant, splice_region_variant	20/23		NM_001393629.1	ENSP00000509157	P5

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

197

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00122

AC:

307

AN:

251452

Hom.:

AF XY:

0.00130

AC XY:

177

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00157

AC:

2286

AN:

1460642

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1177

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.00183

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00130

AC:

197

AN:

152122

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00110

AC:

133

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.2923G>A (p.E975K) alteration is located in exon 16 (coding exon 14) of the RIMBP2 gene. This alteration results from a G to A substitution at nucleotide position 2923, causing the glutamic acid (E) at amino acid position 975 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.060

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.2

D;.

REVEL

Uncertain

0.36

Sift

Benign

0.12

T;.

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

D;.

Vest4

0.83

MVP

0.67

MPC

1.0

ClinPred

0.18

GERP RS

4.9

Varity_R

0.38

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.77

dbscSNV1_RF

Pathogenic

0.75

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