9-126666398-A-G

Variant names:

• chr9-126666398-A-G
• rs4322101
• NM_001174147.2:c.327-24438A>G

Variant summary

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

The NM_001174147.2(LMX1B):​c.327-24438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,024 control chromosomes in the GnomAD database, including 14,934 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 0.44 (14934 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.513 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.327-24438A>G		intron	N/A	NP_001167618.1
	LMX1B	NM_001174146.2		c.327-24438A>G		intron	N/A	NP_001167617.1
	LMX1B	NM_002316.4		c.327-24438A>G		intron	N/A	NP_002307.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.327-24438A>G		intron	N/A	ENSP00000362573.3
	LMX1B	ENST00000355497.10	TSL:1	c.327-24438A>G		intron	N/A	ENSP00000347684.5
	LMX1B	ENST00000526117.6	TSL:1	c.327-24438A>G		intron	N/A	ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66893 AN: 151906 Hom.: 14916 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.440 AC: 66955 AN: 152024 Hom.: 14934 Cov.: 32 AF XY: 0.440 AC XY: 32687 AN XY: 74314

African (AFR) AF: 0.495 AC: 20524 AN: 41474

American (AMR) AF: 0.428 AC: 6539 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2728 AN: 5154

South Asian (SAS) AF: 0.441 AC: 2125 AN: 4816

European-Finnish (FIN) AF: 0.391 AC: 4135 AN: 10562

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28138 AN: 67954

Other (OTH) AF: 0.436 AC: 919 AN: 2108

Alfa AF: 0.411 Hom.: 24226

Bravo AF: 0.445

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.62
PhyloP100		-2.7
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: rs4322101; hg19: chr9-129428677; COSMIC: COSV62738664;