rs10448285

Variant names:

• chr9-126634735-C-T
• rs10448285
• NM_001174147.2:c.326+19166C>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+19166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,972 control chromosomes in the GnomAD database, including 8,284 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 0.32 (8284 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 7 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 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.326+19166C>T		intron	N/A	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.326+19166C>T		intron	N/A	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.326+19166C>T		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.326+19166C>T		intron	N/A	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.326+19166C>T		intron	N/A	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.326+19166C>T		intron	N/A	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49241 AN: 151854 Hom.: 8286 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.324 AC: 49260 AN: 151972 Hom.: 8284 Cov.: 32 AF XY: 0.323 AC XY: 24004 AN XY: 74268

African (AFR) AF: 0.318 AC: 13155 AN: 41430

American (AMR) AF: 0.272 AC: 4165 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1223 AN: 3458

East Asian (EAS) AF: 0.113 AC: 586 AN: 5166

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4818

European-Finnish (FIN) AF: 0.383 AC: 4035 AN: 10542

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23681 AN: 67954

Other (OTH) AF: 0.334 AC: 704 AN: 2108

Alfa AF: 0.338 Hom.: 35138

Bravo AF: 0.312

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-1.5
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: rs10448285; hg19: chr9-129397014; COSMIC: COSV62738606;