1-225412467-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.1071G>A(p.Ser357Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,613,868 control chromosomes in the GnomAD database, including 2,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 151 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1924 hom. )

Consequence

LBR
NM_002296.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.75

Publications

6 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=-0.59).

BP6

Variant 1-225412467-C-T is Benign according to our data. Variant chr1-225412467-C-T is described in ClinVar as Benign. ClinVar VariationId is 295936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.74 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBR	NM_002296.4 link	c.1071G>A	p.Ser357Ser	synonymous_variant	Exon 8 of 14	ENST00000272163.9	NP_002287.2	Q14739

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LBR	ENST00000272163.9 link	c.1071G>A	p.Ser357Ser	synonymous_variant	Exon 8 of 14	1	NM_002296.4	ENSP00000272163.4	Q14739
LBR	ENST00000338179.6 link	c.1071G>A	p.Ser357Ser	synonymous_variant	Exon 8 of 14	5		ENSP00000339883.2	Q14739
LBR	ENST00000651341.1 link	n.1071G>A		non_coding_transcript_exon_variant	Exon 8 of 15			ENSP00000499114.1	A0A494C1L1

Frequencies

GnomAD3 genomes

AF:

0.0401

AC:

6091

AN:

152048

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0303

Gnomad ASJ

AF:

0.0318

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.0888

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0422

GnomAD2 exomes

AF:

0.0466

AC:

11706

AN:

251400

AF XY:

0.0485

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.0254

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.0208

Gnomad FIN exome

AF:

0.0855

Gnomad NFE exome

AF:

0.0530

Gnomad OTH exome

AF:

0.0554

GnomAD4 exome

AF:

0.0493

AC:

72105

AN:

1461702

Hom.:

1924

Cov.:

AF XY:

0.0498

AC XY:

36187

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0148

AC:

494

AN:

33472

American (AMR)

AF:

0.0261

AC:

1168

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0319

AC:

834

AN:

26134

East Asian (EAS)

AF:

0.0311

AC:

1234

AN:

39700

South Asian (SAS)

AF:

0.0561

AC:

4836

AN:

86252

European-Finnish (FIN)

AF:

0.0830

AC:

4433

AN:

53416

Middle Eastern (MID)

AF:

0.0447

AC:

256

AN:

5730

European-Non Finnish (NFE)

AF:

0.0504

AC:

55991

AN:

1111898

Other (OTH)

AF:

0.0474

AC:

2859

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

3460

6921

10381

13842

17302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2084

4168

6252

8336

10420

<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:

0.0402

AC:

6113

AN:

152166

Hom.:

151

Cov.:

AF XY:

0.0418

AC XY:

3107

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0165

AC:

687

AN:

41530

American (AMR)

AF:

0.0303

AC:

464

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

110

AN:

3464

East Asian (EAS)

AF:

0.0234

AC:

121

AN:

5180

South Asian (SAS)

AF:

0.0531

AC:

256

AN:

4822

European-Finnish (FIN)

AF:

0.0888

AC:

938

AN:

10566

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0498

AC:

3384

AN:

68000

Other (OTH)

AF:

0.0498

AC:

105

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

309

618

928

1237

1546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0454

Hom.:

Bravo

AF:

0.0341

Asia WGS

AF:

0.0590

AC:

203

AN:

3478

EpiCase

AF:

0.0490

EpiControl

AF:

0.0536

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

May 05, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Greenberg dysplasia

Benign:1

Jan 13, 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. -

Connective tissue disorder

Benign:1

Jul 14, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.59

CADD

Benign

0.51

(source)

DANN

Benign

0.88

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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