rs911065623

Variant names:

• chr1-225403313-T-A
• rs911065623
• NM_002296.4:c.1838A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-225403313-T-A
• chr1-225403313-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002296.4(LBR):​c.1838A>T​(p.Tyr613Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y613C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LBR NM_002296.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBR	NM_002296.4	c.1838A>T	p.Tyr613Phe	missense_variant	Exon 14 of 14	ENST00000272163.9	NP_002287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBR	ENST00000272163.9	c.1838A>T	p.Tyr613Phe	missense_variant	Exon 14 of 14	1	NM_002296.4	ENSP00000272163.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	9.6
DANN	Benign	0.91
DEOGEN2	Pathogenic	0.96	D;D
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.91	.;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	2.0	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.41
Sift	Benign	0.084	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.064	B;B
Vest4		0.13
MutPred		0.81		Loss of disorder (P = 0.0753);Loss of disorder (P = 0.0753);
MVP		0.59
MPC		0.10
ClinPred		0.24	T
GERP RS		3.9
Varity_R		0.18
gMVP		0.73

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: rs911065623; hg19: chr1-225591015;