rs16844846

Variant names:

• chr1-225405225-T-G
• rs16844846
• NM_002296.4:c.1484-519A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002296.4(LBR):​c.1484-519A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,252 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (177 hom., cov: 32)
• Consequence: LBR NM_002296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
• 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002296.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBR	NM_002296.4	MANE Select	c.1484-519A>C		intron	N/A	NP_002287.2
	LBR	NM_194442.3		c.1484-519A>C		intron	N/A	NP_919424.1	Q14739

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBR	ENST00000272163.9	TSL:1 MANE Select	c.1484-519A>C		intron	N/A	ENSP00000272163.4	Q14739
	LBR	ENST00000338179.6	TSL:5	c.1484-519A>C		intron	N/A	ENSP00000339883.2	Q14739
	LBR	ENST00000885795.1		c.1484-519A>C		intron	N/A	ENSP00000555854.1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6813 AN: 152134 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0507

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0449 AC: 6833 AN: 152252 Hom.: 177 Cov.: 32 AF XY: 0.0467 AC XY: 3480 AN XY: 74440

African (AFR) AF: 0.0252 AC: 1047 AN: 41560

American (AMR) AF: 0.0320 AC: 489 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3470

East Asian (EAS) AF: 0.0656 AC: 339 AN: 5170

South Asian (SAS) AF: 0.0695 AC: 336 AN: 4834

European-Finnish (FIN) AF: 0.0886 AC: 938 AN: 10592

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3402 AN: 68010

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0476 Hom.: 296

Bravo AF: 0.0390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.045
DANN	Benign	0.50
PhyloP100		-1.9
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: rs16844846; hg19: chr1-225592927;