rs367613299

Variant names:

• chr10-101228590-G-A
• rs367613299
• NM_006562.5:c.226C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101228590-G-A
• chr10-101228590-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006562.5(LBX1):​c.226C>T​(p.Arg76Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000244 in 1,556,508 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R76R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08
• Publications: 0 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.226C>T	p.Arg76Cys	missense	Exon 1 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.226C>T	p.Arg76Cys	missense	Exon 1 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.226C>T	p.Arg76Cys	missense	Exon 2 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.226C>T	p.Arg76Cys	missense	Exon 2 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000108 AC: 17 AN: 157130 AF XY: 0.000107

Gnomad AFR exome AF: 0.000128

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000263

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000258 AC: 363 AN: 1404286 Hom.: 2 Cov.: 33 AF XY: 0.000255 AC XY: 177 AN XY: 693084

African (AFR) AF: 0.0000631 AC: 2 AN: 31696

American (AMR) AF: 0.0000279 AC: 1 AN: 35890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25024

East Asian (EAS) AF: 0.00 AC: 0 AN: 36682

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.000308 AC: 333 AN: 1082228

Other (OTH) AF: 0.000447 AC: 26 AN: 58148

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74366

African (AFR) AF: 0.0000723 AC: 3 AN: 41466

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.000110

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000249 AC: 2

ExAC AF: 0.000168 AC: 18

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	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.70	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.43
MVP		0.97
ClinPred		0.36	T
GERP RS		4.2
Varity_R		0.46
gMVP		0.73
Mutation Taster		=54/46	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: rs367613299; hg19: chr10-102988347;