rs12410357

Variant names:

• chr1-225422061-G-A
• rs12410357
• NM_002296.4:c.366+16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.131
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LBR	NM_002296.4	c.366+16C>T		intron_variant	Intron 3 of 13	ENST00000272163.9	NP_002287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBR	ENST00000272163.9	c.366+16C>T		intron_variant	Intron 3 of 13	1	NM_002296.4	ENSP00000272163.4

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14792 AN: 152102 Hom.: 829 Cov.: 33

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

GnomAD2 exomes AF: 0.106 AC: 26480 AN: 250906 AF XY: 0.110

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 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.: 29 AF XY: 0.120 AC XY: 86999 AN XY: 725730

African (AFR) AF: 0.0637 AC: 2130 AN: 33412

American (AMR) AF: 0.0988 AC: 4418 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3752 AN: 26130

East Asian (EAS) AF: 0.0390 AC: 1549 AN: 39682

South Asian (SAS) AF: 0.136 AC: 11682 AN: 86168

European-Finnish (FIN) AF: 0.0696 AC: 3682 AN: 52906

Middle Eastern (MID) AF: 0.129 AC: 730 AN: 5672

European-Non Finnish (NFE) AF: 0.124 AC: 137841 AN: 1109346

Other (OTH) AF: 0.117 AC: 7068 AN: 60304

GnomAD4 genome AF: 0.0972 AC: 14798 AN: 152220 Hom.: 826 Cov.: 33 AF XY: 0.0940 AC XY: 6992 AN XY: 74414

African (AFR) AF: 0.0603 AC: 2507 AN: 41542

American (AMR) AF: 0.102 AC: 1563 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5186

South Asian (SAS) AF: 0.134 AC: 648 AN: 4828

European-Finnish (FIN) AF: 0.0685 AC: 726 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8298 AN: 67990

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.119 Hom.: 1543

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

Submissions by phenotype

not provided Benign:3

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.83
CADD	Benign	7.9
DANN	Benign	0.78
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12410357; hg19: chr1-225609763; COSMIC: COSV55290820; COSMIC: COSV55290820;