rs1011319

chr1-225410144-A-Gchr1-225410144-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.94

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]

ACMG classification

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/exons	MANE	UniProt
LBR	NM_002296.4	c.1314+147T>C		intron_variant		ENST00000272163.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LBR	ENST00000272163.9	c.1314+147T>C		intron_variant		1	NM_002296.4	P1
LBR	ENST00000338179.6	c.1314+147T>C		intron_variant		5		P1
LBR	ENST00000651341.1	c.*480+147T>C		intron_variant, NMD_transcript_variant
LBR	ENST00000424022.2	n.207+147T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112762 AN: 151986 Hom.: 44131 Cov.: 32

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

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.: 32 AF XY: 0.743 AC XY: 55275 AN XY: 74366

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

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

Other links and lift over

dbSNP: rs1011319; hg19: chr1-225597846;