Variant 1-225423959-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002296.4(LBR):c.117G>A(p.Val39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,612,512 control chromosomes in the GnomAD database, including 420,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38834 hom., cov: 32)

Exomes 𝑓: 0.72 ( 381401 hom. )

Consequence

LBR
NM_002296.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.10

Variant links:

Genes affected

LBR (HGNC:6518): (lamin B receptor) The protein encoded by this gene belongs to the ERG4/ERG24 family. It localized in the nuclear envelope inner membrane and anchors the lamina and the heterochromatin to the membrane. It may mediate interaction between chromatin and lamin B. Mutations of this gene has been associated with autosomal recessive HEM/Greenberg skeletal dysplasia. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

LBR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-225423959-C-T is Benign according to our data. Variant chr1-225423959-C-T is described in ClinVar as [Benign]. Clinvar id is 258616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-225423959-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBR	NM_002296.4 linkuse as main transcript	c.117G>A	p.Val39=	synonymous_variant	2/14	ENST00000272163.9	NP_002287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBR	ENST00000272163.9 linkuse as main transcript	c.117G>A	p.Val39=	synonymous_variant	2/14	1	NM_002296.4	ENSP00000272163	P1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108126

AN:

151964

Hom.:

38809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.722

GnomAD3 exomes

AF:

0.718

AC:

180471

AN:

251444

Hom.:

65798

AF XY:

0.706

AC XY:

95912

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.640

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.768

Gnomad SAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.787

Gnomad NFE exome

AF:

0.735

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.720

AC:

1051372

AN:

1460430

Hom.:

381401

Cov.:

AF XY:

0.714

AC XY:

518598

AN XY:

726598

show subpopulations

Gnomad4 AFR exome

AF:

0.640

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.746

Gnomad4 EAS exome

AF:

0.773

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.729

Gnomad4 OTH exome

AF:

0.721

GnomAD4 genome

AF:

0.711

AC:

108193

AN:

152082

Hom.:

38834

Cov.:

AF XY:

0.713

AC XY:

52963

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.638

Gnomad4 AMR

AF:

0.774

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.760

Gnomad4 SAS

AF:

0.509

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.737

Gnomad4 OTH

AF:

0.725

Alfa

AF:

0.721

Hom.:

33093

Bravo

AF:

0.713

Asia WGS

AF:

0.635

AC:

2210

AN:

3478

EpiCase

AF:

0.735

EpiControl

AF:

0.738

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 06, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 71% of total chromosomes in ExAC -

Greenberg dysplasia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Reynolds syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Pelger-Huët anomaly

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.43

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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