Variant 5-36105152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000296603.5(LMBRD2):c.1943G>A(p.Arg648Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,612,510 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R648W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

LMBRD2
ENST00000296603.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.53

Variant links:

Genes affected

LMBRD2 (HGNC:25287): (LMBR1 domain containing 2) Involved in adrenergic receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LMBRD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011989623).

BP6

Variant 5-36105152-C-T is Benign according to our data. Variant chr5-36105152-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050035.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LMBRD2	NM_001007527.2 linkuse as main transcript	c.1943G>A	p.Arg648Gln	missense_variant	17/18	ENST00000296603.5	NP_001007528.1
LMBRD2	XM_011514162.3 linkuse as main transcript	c.1943G>A	p.Arg648Gln	missense_variant	17/18		XP_011512464.1
LMBRD2	XM_047417877.1 linkuse as main transcript	c.1280G>A	p.Arg427Gln	missense_variant	13/14		XP_047273833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5 linkuse as main transcript	c.1943G>A	p.Arg648Gln	missense_variant	17/18	1	NM_001007527.2	ENSP00000296603	P1

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

207

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00163

AC:

410

AN:

250772

Hom.:

AF XY:

0.00166

AC XY:

225

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00224

AC:

3266

AN:

1460402

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1563

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00262

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00136

AC:

207

AN:

152108

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00139

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00155

AC:

188

EpiCase

AF:

0.00284

EpiControl

AF:

0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LMBRD2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

0.033

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0037

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.76

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Benign

0.12

Polyphen

0.0030

Vest4

0.60

MVP

0.51

MPC

0.36

ClinPred

0.020

GERP RS

5.4

Varity_R

0.13

gMVP

0.35

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