rs2235056

Variant names:

• chr9-126614956-C-T
• rs2235056
• NM_001174147.2:c.139+368C>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.139+368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,108 control chromosomes in the GnomAD database, including 1,357 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 0.10 (1357 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 10 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 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.139+368C>T		intron	N/A	NP_001167618.1
	LMX1B	NM_001174146.2		c.139+368C>T		intron	N/A	NP_001167617.1
	LMX1B	NM_002316.4		c.139+368C>T		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.139+368C>T		intron	N/A	ENSP00000362573.3
	LMX1B	ENST00000355497.10	TSL:1	c.139+368C>T		intron	N/A	ENSP00000347684.5
	LMX1B	ENST00000526117.6	TSL:1	c.139+368C>T		intron	N/A	ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15665 AN: 151990 Hom.: 1338 Cov.: 31

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.103 AC: 15702 AN: 152108 Hom.: 1357 Cov.: 31 AF XY: 0.109 AC XY: 8130 AN XY: 74346

African (AFR) AF: 0.0646 AC: 2681 AN: 41526

American (AMR) AF: 0.222 AC: 3393 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2263 AN: 5106

South Asian (SAS) AF: 0.188 AC: 908 AN: 4818

European-Finnish (FIN) AF: 0.0809 AC: 858 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0721 AC: 4899 AN: 67976

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.0892 Hom.: 1686

Bravo AF: 0.115

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2235056; hg19: chr9-129377235;