chr1-225405225-T-G

Position:

• chr1-225405225-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LBR	NM_002296.4	c.1484-519A>C		intron_variant		ENST00000272163.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LBR	ENST00000272163.9	c.1484-519A>C		intron_variant		1	NM_002296.4	P1
LBR	ENST00000338179.6	c.1484-519A>C		intron_variant		5		P1
LBR	ENST00000651341.1	c.*650-519A>C		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.0656

Gnomad4 SAS AF: 0.0695

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0467 Hom.: 18

Bravo AF: 0.0390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.045
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs16844846; hg19: chr1-225592927;