NM_001174147.2:c.326+36455G>T

Variant names:

• chr9-126652024-G-T
• rs12555176
• NM_001174147.2:c.326+36455G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174147.2(LMX1B):​c.326+36455G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 150,916 control chromosomes in the GnomAD database, including 293 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 0.057 (293 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 2 publications found

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]

LMX1B Gene-Disease associations (from GenCC):

• nail-patella syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• nail-patella-like renal disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+36455G>T		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+36455G>T		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+36455G>T		intron_variant	Intron 2 of 7		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+36455G>T		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+36455G>T		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+36455G>T		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8592 AN: 150804 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0806

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0422

Gnomad EAS AF: 0.00338

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.0649

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0721

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

GnomAD4 genome AF: 0.0569 AC: 8590 AN: 150916 Hom.: 293 Cov.: 31 AF XY: 0.0550 AC XY: 4050 AN XY: 73654

African (AFR) AF: 0.0154 AC: 633 AN: 41048

American (AMR) AF: 0.0626 AC: 949 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 146 AN: 3458

East Asian (EAS) AF: 0.00318 AC: 16 AN: 5024

South Asian (SAS) AF: 0.0384 AC: 182 AN: 4738

European-Finnish (FIN) AF: 0.0697 AC: 728 AN: 10442

Middle Eastern (MID) AF: 0.0660 AC: 19 AN: 288

European-Non Finnish (NFE) AF: 0.0841 AC: 5696 AN: 67758

Other (OTH) AF: 0.0708 AC: 148 AN: 2090

Alfa AF: 0.0630 Hom.: 178

Bravo AF: 0.0524

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.081
Mutation Taster		=100/0	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: rs12555176; hg19: chr9-129414303;