Genetic Variant LBX1:p.Asp274Asn (chr10-101227296-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006562.5(LBX1):c.820G>A(p.Asp274Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,455,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

LBX1
NM_006562.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Publications

0 publications found

Variant links:

Genes affected

LBX1 (HGNC:16960): (ladybird homeobox 1) This gene and the orthologous mouse gene were found by their homology to the Drosophila lady bird early and late homeobox genes. In the mouse, this gene is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles. [provided by RefSeq, Jul 2008]

LBX1 links:

LBX1-AS1 (HGNC:48678): (LBX1 antisense RNA 1)

LBX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006562.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBX1	NM_006562.5	MANE Select	c.820G>A	p.Asp274Asn	missense	Exon 2 of 2	NP_006553.2	P52954

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LBX1	ENST00000370193.4	TSL:1 MANE Select	c.820G>A	p.Asp274Asn	missense	Exon 2 of 2	ENSP00000359212.2	P52954
LBX1	ENST00000945825.1		c.820G>A	p.Asp274Asn	missense	Exon 3 of 3	ENSP00000615884.1
LBX1	ENST00000945826.1		c.820G>A	p.Asp274Asn	missense	Exon 3 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000424

AC:

AN:

235912

AF XY:

0.0000619

show subpopulations

Gnomad AFR exome

AF:

0.0000713

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000387

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000632

AC:

AN:

1455016

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

723886

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32448

American (AMR)

AF:

0.000135

AC:

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

38938

South Asian (SAS)

AF:

0.00

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5178

European-Non Finnish (NFE)

AF:

0.0000766

AC:

AN:

1110174

Other (OTH)

AF:

0.00

AC:

AN:

60046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.70

MetaRNN

Uncertain

0.55

MetaSVM

Pathogenic

0.96

MutationAssessor

Uncertain

2.2

PhyloP100

1.5

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.29

MVP

0.91

ClinPred

0.28

GERP RS

5.8

Varity_R

0.51

gMVP

0.36

Mutation Taster

=53/47

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over