rs10760444

Positions:

• chr9-126634155-G-A

Variant summary

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

The ENST00000373474.9(LMX1B):​c.326+18586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,000 control chromosomes in the GnomAD database, including 20,035 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 0.51 (20035 hom., cov: 32)
• Consequence: LMX1B ENST00000373474.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+18586G>A		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+18586G>A		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.326+18586G>A		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+18586G>A		intron_variant		1	NM_001174147.2	ENSP00000362573	P4
LMX1B	ENST00000355497.10	c.326+18586G>A		intron_variant		1		ENSP00000347684
LMX1B	ENST00000526117.6	c.326+18586G>A		intron_variant		1		ENSP00000436930	A1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77503 AN: 151882 Hom.: 20035 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.510 AC: 77525 AN: 152000 Hom.: 20035 Cov.: 32 AF XY: 0.506 AC XY: 37558 AN XY: 74294

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.492

Alfa AF: 0.550 Hom.: 24508

Bravo AF: 0.505

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.021
DANN	Benign	0.42

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: rs10760444; hg19: chr9-129396434;