chr1-225412467-C-T

Position:

chr1-225412467-C-T

Variant summary

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

The NM_002296.4(LBR):c.1071G>A(p.Ser357=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 295936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-225412467-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
LBR	NM_002296.4 linkuse as main transcript	c.1071G>A	p.Ser357=	synonymous_variant	8/14	ENST00000272163.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LBR	ENST00000272163.9 linkuse as main transcript	c.1071G>A	p.Ser357=	synonymous_variant	8/14	1	NM_002296.4	P1
LBR	ENST00000338179.6 linkuse as main transcript	c.1071G>A	p.Ser357=	synonymous_variant	8/14	5		P1
LBR	ENST00000651341.1 linkuse as main transcript	c.1071G>A	p.Ser357=	synonymous_variant, NMD_transcript_variant	8/15

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

GnomAD3 exomes

AF:

0.0466

AC:

11706

AN:

251400

Hom.:

353

AF XY:

0.0485

AC XY:

6593

AN XY:

135874

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 SAS exome

AF:

0.0546

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

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.0261

Gnomad4 ASJ exome

AF:

0.0319

Gnomad4 EAS exome

AF:

0.0311

Gnomad4 SAS exome

AF:

0.0561

Gnomad4 FIN exome

AF:

0.0830

Gnomad4 NFE exome

AF:

0.0504

Gnomad4 OTH exome

AF:

0.0474

GnomAD4 genome

AF:

0.0402

AC:

6113

AN:

152166

Hom.:

151

Cov.:

AF XY:

0.0418

AC XY:

3107

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.0318

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.0531

Gnomad4 FIN

AF:

0.0888

Gnomad4 NFE

AF:

0.0498

Gnomad4 OTH

AF:

0.0498

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

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Greenberg dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.51

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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