rs199819784

Variant names:

• chr10-101227403-G-T
• rs199819784
• NM_006562.5:c.713C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006562.5(LBX1):​c.713C>A​(p.Pro238His) variant causes a missense change. The variant allele was found at a frequency of 0.000408 in 1,601,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P238P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14458555).

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.713C>A	p.Pro238His	missense	Exon 2 of 2	NP_006553.2	P52954

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBX1	ENST00000370193.4	TSL:1 MANE Select	c.713C>A	p.Pro238His	missense	Exon 2 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.713C>A	p.Pro238His	missense	Exon 3 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.713C>A	p.Pro238His	missense	Exon 3 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000356 AC: 79 AN: 221888 AF XY: 0.000389

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000107

Gnomad NFE exome AF: 0.000542

Gnomad OTH exome AF: 0.000363

GnomAD4 exome AF: 0.000415 AC: 601 AN: 1449448 Hom.: 1 Cov.: 31 AF XY: 0.000466 AC XY: 336 AN XY: 720730

African (AFR) AF: 0.0000303 AC: 1 AN: 32962

American (AMR) AF: 0.000275 AC: 12 AN: 43704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.000327 AC: 28 AN: 85606

European-Finnish (FIN) AF: 0.0000817 AC: 4 AN: 48930

Middle Eastern (MID) AF: 0.00443 AC: 21 AN: 4738

European-Non Finnish (NFE) AF: 0.000456 AC: 506 AN: 1108486

Other (OTH) AF: 0.000485 AC: 29 AN: 59768

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74494

African (AFR) AF: 0.0000240 AC: 1 AN: 41586

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000472 Hom.: 0

Bravo AF: 0.000359

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000246 AC: 2

ExAC AF: 0.000305 AC: 36

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	1.0	L
PhyloP100		4.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.30
Sift	Benign	0.18	T
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.26
MVP		0.86
ClinPred		0.062	T
GERP RS		5.5
Varity_R		0.15
gMVP		0.28
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs199819784; hg19: chr10-102987160;