rs12555734

Variant names:

• chr9-126648963-C-A
• rs12555734
• NM_001174147.2:c.326+33394C>A

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+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
• Publications: 1 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=-0.84).
• 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 rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+33394C>A		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+33394C>A		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+33394C>A		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+33394C>A		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+33394C>A		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+33394C>A		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

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

African (AFR) AF: 0.0418 AC: 1737 AN: 41520

American (AMR) AF: 0.150 AC: 2293 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3466

East Asian (EAS) AF: 0.00946 AC: 49 AN: 5178

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4794

European-Finnish (FIN) AF: 0.306 AC: 3230 AN: 10558

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16997 AN: 67940

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.209 Hom.: 6399

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
PhyloP100		-0.20
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: rs12555734; hg19: chr9-129411242;