1-225410144-A-C

Variant names:

• chr1-225410144-A-C
• rs1011319
• NM_002296.4:c.1314+147T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002296.4(LBR):​c.1314+147T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000968 in 1,033,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: LBR NM_002296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.94
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBR	NM_002296.4	MANE Select	c.1314+147T>G		intron	N/A	NP_002287.2
	LBR	NM_194442.3		c.1314+147T>G		intron	N/A	NP_919424.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBR	ENST00000272163.9	TSL:1 MANE Select	c.1314+147T>G		intron	N/A	ENSP00000272163.4
	LBR	ENST00000338179.6	TSL:5	c.1314+147T>G		intron	N/A	ENSP00000339883.2
	LBR	ENST00000424022.2	TSL:3	n.207+147T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.68e-7 AC: 1 AN: 1033416 Hom.: 0 AF XY: 0.00000189 AC XY: 1 AN XY: 529156

African (AFR) AF: 0.00 AC: 0 AN: 24396

American (AMR) AF: 0.00 AC: 0 AN: 39014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22256

East Asian (EAS) AF: 0.00 AC: 0 AN: 35484

South Asian (SAS) AF: 0.00 AC: 0 AN: 74878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3626

European-Non Finnish (NFE) AF: 0.00000133 AC: 1 AN: 750538

Other (OTH) AF: 0.00 AC: 0 AN: 45800

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.020
DANN	Benign	0.39
PhyloP100		-5.9

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: rs1011319; hg19: chr1-225597846;