9-126655530-G-C

Variant names:

• chr9-126655530-G-C
• rs12551234
• NM_001174147.2:c.327-35306G>C

Variant summary

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

The NM_001174147.2(LMX1B):​c.327-35306G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,004 control chromosomes in the GnomAD database, including 12,710 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 0.40 (12710 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174147.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.327-35306G>C		intron	N/A	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.327-35306G>C		intron	N/A	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.327-35306G>C		intron	N/A	NP_002307.2	O60663-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.327-35306G>C		intron	N/A	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.327-35306G>C		intron	N/A	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.327-35306G>C		intron	N/A	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60029 AN: 151886 Hom.: 12691 Cov.: 31

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.395 AC: 60080 AN: 152004 Hom.: 12710 Cov.: 31 AF XY: 0.386 AC XY: 28668 AN XY: 74296

African (AFR) AF: 0.481 AC: 19946 AN: 41436

American (AMR) AF: 0.270 AC: 4129 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3468

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5190

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4818

European-Finnish (FIN) AF: 0.322 AC: 3403 AN: 10552

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28356 AN: 67948

Other (OTH) AF: 0.351 AC: 742 AN: 2112

Alfa AF: 0.281 Hom.: 704

Bravo AF: 0.388

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.30
PhyloP100		-1.1
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: rs12551234; hg19: chr9-129417809;