Variant chr1-225401771-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002296.4(LBR):c.*1532G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,100 control chromosomes in the GnomAD database, including 6,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6972 hom., cov: 32)

Exomes 𝑓: 0.33 ( 1 hom. )

Consequence

LBR
NM_002296.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.785

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 -20 ACMG points.

BP4

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

BP6

Variant 1-225401771-C-T is Benign according to our data. Variant chr1-225401771-C-T is described in ClinVar as [Benign]. Clinvar id is 295917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBR	NM_002296.4 link	c.*1532G>A		3_prime_UTR_variant	14/14	ENST00000272163.9	NP_002287.2	Q14739

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LBR	ENST00000272163 link	c.*1532G>A	3_prime_UTR_variant	14/14	1	NM_002296.4	ENSP00000272163.4	Q14739
LBR	ENST00000338179 link	c.*1532G>A	3_prime_UTR_variant	14/14	5		ENSP00000339883.2	Q14739
LBR	ENST00000651341.1 link	n.*1114-43G>A	intron_variant				ENSP00000499114.1	A0A494C1L1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38403

AN:

151976

Hom.:

6962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.0423

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.253

AC:

38441

AN:

152094

Hom.:

6972

Cov.:

AF XY:

0.252

AC XY:

18699

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.0421

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.169

Hom.:

3497

Bravo

AF:

0.261

Asia WGS

AF:

0.172

AC:

598

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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