Variant chr5-36108536-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000296603.5(LMBRD2):c.1895G>A(p.Arg632His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000696 in 1,508,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R632C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

LMBRD2
ENST00000296603.5 missense, splice_region

Scores

Splicing: ADA: 0.1011

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1314336).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LMBRD2	NM_001007527.2 linkuse as main transcript	c.1895G>A	p.Arg632His	missense_variant, splice_region_variant	16/18	ENST00000296603.5	NP_001007528.1
LMBRD2	XM_011514162.3 linkuse as main transcript	c.1895G>A	p.Arg632His	missense_variant, splice_region_variant	16/18		XP_011512464.1
LMBRD2	XM_047417877.1 linkuse as main transcript	c.1232G>A	p.Arg411His	missense_variant, splice_region_variant	12/14		XP_047273833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5 linkuse as main transcript	c.1895G>A	p.Arg632His	missense_variant, splice_region_variant	16/18	1	NM_001007527.2	ENSP00000296603	P1
LMBRD2	ENST00000505524.1 linkuse as main transcript	n.356G>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000297

AC:

AN:

235296

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000655

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:

0.0000460

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000701

AC:

AN:

1355940

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

676042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000488

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000526

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000814

Gnomad4 OTH exome

AF:

0.0000715

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.1895G>A (p.R632H) alteration is located in exon 16 (coding exon 15) of the LMBRD2 gene. This alteration results from a G to A substitution at nucleotide position 1895, causing the arginine (R) at amino acid position 632 to be replaced by a histidine (H). 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

Benign

0.086

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.012

Eigen_PC

Benign

0.095

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.71

M_CAP

Benign

0.0048

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.81

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.60

REVEL

Benign

0.096

Sift

Benign

0.093

Sift4G

Uncertain

0.059

Polyphen

0.52

Vest4

0.21

MVP

0.58

MPC

0.46

ClinPred

0.27

GERP RS

4.9

Varity_R

0.047

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.10

dbscSNV1_RF

Benign

0.29

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