rs12555734

chr9-126648963-C-A

Variant summary

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

The NM_001174147.2(LMX1B):c.326+33394C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,058 control chromosomes in the GnomAD database, including 3,167 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 0.18 (3167 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1B	NM_001174147.2	c.326+33394C>A		intron_variant		ENST00000373474.9
LMX1B	NM_001174146.2	c.326+33394C>A		intron_variant
LMX1B	NM_002316.4	c.326+33394C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+33394C>A		intron_variant		1	NM_001174147.2	P4
LMX1B	ENST00000355497.10	c.326+33394C>A		intron_variant		1
LMX1B	ENST00000526117.6	c.326+33394C>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27045 AN: 151940 Hom.: 3169 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.178 AC: 27034 AN: 152058 Hom.: 3167 Cov.: 32 AF XY: 0.178 AC XY: 13238 AN XY: 74300

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.164

Alfa AF: 0.226 Hom.: 766

Bravo AF: 0.157

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.1
Dann	Benign	0.79

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: rs12555734; hg19: chr9-129411242;