10-101228588-G-A

Variant names:

• chr10-101228588-G-A
• rs941909
• NM_006562.5:c.228C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006562.5(LBX1):​c.228C>T​(p.Arg76Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,555,180 control chromosomes in the GnomAD database, including 56,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3928 hom., cov: 33)
  • Exomes 𝑓: 0.26 (52541 hom.)
• Consequence: LBX1 NM_006562.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.714
• Publications: 10 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-101228588-G-A is Benign according to our data. Variant chr10-101228588-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.714 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

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.228C>T	p.Arg76Arg	synonymous	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.228C>T	p.Arg76Arg	synonymous	Exon 1 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.228C>T	p.Arg76Arg	synonymous	Exon 2 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.228C>T	p.Arg76Arg	synonymous	Exon 2 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31695 AN: 152126 Hom.: 3925 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.204

GnomAD2 exomes AF: 0.205 AC: 32014 AN: 155802 AF XY: 0.202

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.0607

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.263 AC: 369458 AN: 1402942 Hom.: 52541 Cov.: 34 AF XY: 0.258 AC XY: 178783 AN XY: 692330

African (AFR) AF: 0.102 AC: 3238 AN: 31640

American (AMR) AF: 0.163 AC: 5862 AN: 35854

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 4959 AN: 25002

East Asian (EAS) AF: 0.0579 AC: 2121 AN: 36616

South Asian (SAS) AF: 0.0901 AC: 7195 AN: 79832

European-Finnish (FIN) AF: 0.244 AC: 11913 AN: 48882

Middle Eastern (MID) AF: 0.115 AC: 655 AN: 5682

European-Non Finnish (NFE) AF: 0.296 AC: 319708 AN: 1081360

Other (OTH) AF: 0.238 AC: 13807 AN: 58074

GnomAD4 genome AF: 0.208 AC: 31702 AN: 152238 Hom.: 3928 Cov.: 33 AF XY: 0.203 AC XY: 15079 AN XY: 74436

African (AFR) AF: 0.109 AC: 4543 AN: 41574

American (AMR) AF: 0.184 AC: 2822 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3466

East Asian (EAS) AF: 0.0518 AC: 267 AN: 5158

South Asian (SAS) AF: 0.0830 AC: 401 AN: 4834

European-Finnish (FIN) AF: 0.244 AC: 2584 AN: 10608

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19748 AN: 67980

Other (OTH) AF: 0.205 AC: 433 AN: 2116

Alfa AF: 0.259 Hom.: 1819

Bravo AF: 0.202

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		0.71
Mutation Taster		=99/1	polymorphism (auto)

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: rs941909; hg19: chr10-102988345; COSMIC: COSV64621507; COSMIC: COSV64621507;