Genetic Variant LBR:c.1314+147T>C (chr1-225410144-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002296.4(LBR):c.1314+147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,183,924 control chromosomes in the GnomAD database, including 400,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 44157 hom., cov: 32)

Exomes 𝑓: 0.83 ( 356383 hom. )

Consequence

LBR
NM_002296.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.94

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-225410144-A-G is Benign according to our data. Variant chr1-225410144-A-G is described in ClinVar as [Benign]. Clinvar id is 1225790.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBR	NM_002296.4 link	c.1314+147T>C		intron_variant	Intron 10 of 13	ENST00000272163.9	NP_002287.2	Q14739

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LBR	ENST00000272163.9 link	c.1314+147T>C	intron_variant	Intron 10 of 13	1	NM_002296.4	ENSP00000272163.4	Q14739
LBR	ENST00000338179.6 link	c.1314+147T>C	intron_variant	Intron 10 of 13	5		ENSP00000339883.2	Q14739
LBR	ENST00000424022.2 link	n.207+147T>C	intron_variant	Intron 2 of 2	3
LBR	ENST00000651341.1 link	n.*480+147T>C	intron_variant	Intron 10 of 14			ENSP00000499114.1	A0A494C1L1

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112762

AN:

151986

Hom.:

44131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.856

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.957

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.792

GnomAD4 exome

AF:

0.827

AC:

853387

AN:

1031820

Hom.:

356383

AF XY:

0.823

AC XY:

434998

AN XY:

528358

show subpopulations

Gnomad4 AFR exome

AF:

0.460

Gnomad4 AMR exome

AF:

0.873

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

0.963

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.861

Gnomad4 NFE exome

AF:

0.840

Gnomad4 OTH exome

AF:

0.827

GnomAD4 genome

AF:

0.742

AC:

112835

AN:

152104

Hom.:

44157

Cov.:

AF XY:

0.743

AC XY:

55275

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.856

Gnomad4 ASJ

AF:

0.882

Gnomad4 EAS

AF:

0.958

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.862

Gnomad4 NFE

AF:

0.840

Gnomad4 OTH

AF:

0.796

Alfa

AF:

0.787

Hom.:

6014

Bravo

AF:

0.733

Asia WGS

AF:

0.827

AC:

2877

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 09, 2018

GeneDx

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

-0.91

CADD

Benign

0.026

DANN

Benign

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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