chr1-225422182-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002296.4(LBR):c.261T>C(p.Pro87Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,613,514 control chromosomes in the GnomAD database, including 482,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 38108 hom., cov: 31)

Exomes 𝑓: 0.78 ( 444240 hom. )

Consequence

LBR
NM_002296.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.786

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

Greenberg dysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Pelger-Huet anomaly
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
regressive spondylometaphyseal dysplasia
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

LBR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-225422182-A-G is Benign according to our data. Variant chr1-225422182-A-G is described in ClinVar as [Benign]. Clinvar id is 258617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.786 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBR	NM_002296.4 link	c.261T>C	p.Pro87Pro	synonymous_variant	Exon 3 of 14	ENST00000272163.9	NP_002287.2	Q14739

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBR	ENST00000272163.9 link	c.261T>C	p.Pro87Pro	synonymous_variant	Exon 3 of 14	1	NM_002296.4	ENSP00000272163.4		Q14739

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

103922

AN:

151922

Hom.:

38101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.892

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.838

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.732

GnomAD2 exomes

AF:

0.763

AC:

191794

AN:

251336

AF XY:

0.761

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.848

Gnomad ASJ exome

AF:

0.863

Gnomad EAS exome

AF:

0.897

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.787

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.776

AC:

1133824

AN:

1461474

Hom.:

444240

Cov.:

AF XY:

0.773

AC XY:

562047

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.377

AC:

12603

AN:

33472

American (AMR)

AF:

0.844

AC:

37725

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

22454

AN:

26136

East Asian (EAS)

AF:

0.908

AC:

36040

AN:

39698

South Asian (SAS)

AF:

0.652

AC:

56269

AN:

86246

European-Finnish (FIN)

AF:

0.775

AC:

41374

AN:

53362

Middle Eastern (MID)

AF:

0.826

AC:

4640

AN:

5618

European-Non Finnish (NFE)

AF:

0.788

AC:

875935

AN:

1111844

Other (OTH)

AF:

0.775

AC:

46784

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

14430

28861

43291

57722

72152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.684

AC:

103960

AN:

152040

Hom.:

38108

Cov.:

AF XY:

0.684

AC XY:

50812

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.394

AC:

16307

AN:

41430

American (AMR)

AF:

0.818

AC:

12519

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

2973

AN:

3472

East Asian (EAS)

AF:

0.893

AC:

4625

AN:

5182

South Asian (SAS)

AF:

0.650

AC:

3128

AN:

4812

European-Finnish (FIN)

AF:

0.774

AC:

8155

AN:

10538

Middle Eastern (MID)

AF:

0.836

AC:

244

AN:

292

European-Non Finnish (NFE)

AF:

0.791

AC:

53815

AN:

67992

Other (OTH)

AF:

0.728

AC:

1537

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1416

2831

4247

5662

7078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.769

Hom.:

14721

Bravo

AF:

0.678

Asia WGS

AF:

0.747

AC:

2598

AN:

3478

EpiCase

AF:

0.797

EpiControl

AF:

0.795

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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: 75% of total chromosomes in ExAC -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Greenberg dysplasia

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Reynolds syndrome

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pelger-Huët anomaly

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.2

(source)

DANN

Benign

0.58

PhyloP100

-0.79

Mutation Taster

=78/22

polymorphism

(source)

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

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chr1-225422182-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over