1-225404530-TATAAAA-T

Position:

• chr1-225404530-TATAAAA-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_002296.4(LBR):​c.1565-10_1565-5delTTTTAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LBR NM_002296.4 splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.82

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-225404530-TATAAAA-T is Pathogenic according to our data. Variant chr1-225404530-TATAAAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 9527.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBR	NM_002296.4	c.1565-10_1565-5delTTTTAT		splice_region_variant, intron_variant		ENST00000272163.9	NP_002287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBR	ENST00000272163.9	c.1565-10_1565-5delTTTTAT		splice_region_variant, intron_variant		1	NM_002296.4	ENSP00000272163.4
LBR	ENST00000338179.6	c.1565-10_1565-5delTTTTAT		splice_region_variant, intron_variant		5		ENSP00000339883.2
LBR	ENST00000441022.1	n.30_35delTTTTAT		non_coding_transcript_exon_variant	1/2	2
LBR	ENST00000651341.1	n.*731-10_*731-5delTTTTAT		splice_region_variant, intron_variant				ENSP00000499114.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

RHIZOMELIC SKELETAL DYSPLASIA WITH PELGER-HUET ANOMALY Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2002

- -

Pelger-Huët anomaly Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886037616; hg19: chr1-225592232;