Variant chr1-225422061-G-A 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.366+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,610,556 control chromosomes in the GnomAD database, including 11,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 826 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10854 hom. )

Consequence

LBR
NM_002296.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.131

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=-0.83).

BP6

Variant 1-225422061-G-A is Benign according to our data. Variant chr1-225422061-G-A is described in ClinVar as [Benign]. Clinvar id is 258618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBR	NM_002296.4 linkuse as main transcript	c.366+16C>T		intron_variant		ENST00000272163.9	NP_002287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBR	ENST00000272163.9 linkuse as main transcript	c.366+16C>T		intron_variant		1	NM_002296.4	ENSP00000272163	P1

Frequencies

GnomAD3 genomes

AF:

0.0973

AC:

14792

AN:

152102

Hom.:

829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0603

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.106

AC:

26480

AN:

250906

Hom.:

1561

AF XY:

0.110

AC XY:

14895

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.0969

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.0389

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.119

AC:

172852

AN:

1458336

Hom.:

10854

Cov.:

AF XY:

0.120

AC XY:

86999

AN XY:

725730

show subpopulations

Gnomad4 AFR exome

AF:

0.0637

Gnomad4 AMR exome

AF:

0.0988

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.0390

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0696

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0972

AC:

14798

AN:

152220

Hom.:

826

Cov.:

AF XY:

0.0940

AC XY:

6992

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0603

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.0401

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.121

Hom.:

1233

Bravo

AF:

0.0966

Asia WGS

AF:

0.0960

AC:

333

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.9

DANN

Benign

0.78

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