chr9-126651019-C-T

Variant names:

• chr9-126651019-C-T
• rs13285227
• NM_001174147.2:c.326+35450C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001174147.2(LMX1B):​c.326+35450C>T variant causes a intron change. The variant allele was found at a frequency of 0.343 in 151,968 control chromosomes in the GnomAD database, including 9,611 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 0.34 (9611 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30
• 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: 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+35450C>T		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+35450C>T		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+35450C>T		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+35450C>T		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+35450C>T		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+35450C>T		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52095 AN: 151850 Hom.: 9596 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.343 AC: 52130 AN: 151968 Hom.: 9611 Cov.: 32 AF XY: 0.355 AC XY: 26346 AN XY: 74284

African (AFR) AF: 0.234 AC: 9685 AN: 41424

American (AMR) AF: 0.473 AC: 7232 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1306 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2862 AN: 5146

South Asian (SAS) AF: 0.404 AC: 1947 AN: 4822

European-Finnish (FIN) AF: 0.431 AC: 4558 AN: 10570

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23264 AN: 67948

Other (OTH) AF: 0.401 AC: 845 AN: 2106

Alfa AF: 0.345 Hom.: 22749

Bravo AF: 0.342

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Benign	0.79
PhyloP100		4.3
Mutation Taster		=99/1	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: rs13285227; hg19: chr9-129413298;