1-225423959-C-T

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.117G>A(p.Val39Val) 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

Publications

31 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=-0.54).

BP6

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

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 rank	MANE	Protein	UniProt
LBR	NM_002296.4 link	c.117G>A	p.Val39Val	synonymous_variant	Exon 2 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.117G>A	p.Val39Val	synonymous_variant	Exon 2 of 14	1	NM_002296.4	ENSP00000272163.4		Q14739

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

GnomAD2 exomes

AF:

0.718

AC:

180471

AN:

251444

AF XY:

0.706

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 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

African (AFR)

AF:

0.640

AC:

21394

AN:

33440

American (AMR)

AF:

0.784

AC:

35081

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

19500

AN:

26126

East Asian (EAS)

AF:

0.773

AC:

30668

AN:

39690

South Asian (SAS)

AF:

0.522

AC:

45004

AN:

86228

European-Finnish (FIN)

AF:

0.784

AC:

41879

AN:

53410

Middle Eastern (MID)

AF:

0.748

AC:

4313

AN:

5768

European-Non Finnish (NFE)

AF:

0.729

AC:

810057

AN:

1110706

Other (OTH)

AF:

0.721

AC:

43476

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15645

31291

46936

62582

78227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19932

39864

59796

79728

99660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.711

AC:

108193

AN:

152082

Hom.:

38834

Cov.:

AF XY:

0.713

AC XY:

52963

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.638

AC:

26457

AN:

41458

American (AMR)

AF:

0.774

AC:

11839

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2587

AN:

3472

East Asian (EAS)

AF:

0.760

AC:

3933

AN:

5172

South Asian (SAS)

AF:

0.509

AC:

2454

AN:

4824

European-Finnish (FIN)

AF:

0.795

AC:

8385

AN:

10542

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.737

AC:

50124

AN:

68004

Other (OTH)

AF:

0.725

AC:

1534

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1582

3164

4747

6329

7911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.723

Hom.:

39977

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

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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 06, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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: 71% of total chromosomes in ExAC -

Greenberg dysplasia

Benign:2

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. -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.54

CADD

Benign

0.43

(source)

DANN

Benign

0.73

PhyloP100

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

(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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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