rs10987386

chr9-126654038-C-T

Variant summary

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

The NM_001174147.2(LMX1B):c.327-36798C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,086 control chromosomes in the GnomAD database, including 2,590 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 (2590 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1B	NM_001174147.2	c.327-36798C>T		intron_variant		ENST00000373474.9
LMX1B	NM_001174146.2	c.327-36798C>T		intron_variant
LMX1B	NM_002316.4	c.327-36798C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1B	ENST00000373474.9	c.327-36798C>T		intron_variant		1	NM_001174147.2	P4
LMX1B	ENST00000355497.10	c.327-36798C>T		intron_variant		1
LMX1B	ENST00000526117.6	c.327-36798C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27198 AN: 151968 Hom.: 2591 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.179 AC: 27203 AN: 152086 Hom.: 2590 Cov.: 32 AF XY: 0.177 AC XY: 13196 AN XY: 74350

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.178

Alfa AF: 0.194 Hom.: 3866

Bravo AF: 0.169

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.38

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: rs10987386; hg19: chr9-129416317;