rs10732392

Positions:

• chr9-126633758-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174147.2(LMX1B):​c.326+18189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,138 control chromosomes in the GnomAD database, including 53,795 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53795 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

Genes affected

LMX1B (HGNC:6654): (LIM homeobox transcription factor 1 beta) This gene encodes a member of LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+18189A>G		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+18189A>G		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.326+18189A>G		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+18189A>G		intron_variant		1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+18189A>G		intron_variant		1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+18189A>G		intron_variant		1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127067 AN: 152020 Hom.: 53788 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.839

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.835 AC: 127108 AN: 152138 Hom.: 53795 Cov.: 31 AF XY: 0.830 AC XY: 61740 AN XY: 74376

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.829

Alfa AF: 0.848 Hom.: 9703

Bravo AF: 0.817

Asia WGS AF: 0.642 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.31

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: rs10732392; hg19: chr9-129396037;