NM_001174147.2:c.326+12952C>T

Variant names:

• chr9-126628521-C-T
• rs3829849
• NM_001174147.2:c.326+12952C>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+12952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,106 control chromosomes in the GnomAD database, including 6,929 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 0.28 (6929 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737
• Publications: 36 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+12952C>T		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+12952C>T		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+12952C>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+12952C>T		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+12952C>T		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+12952C>T		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43002 AN: 151988 Hom.: 6931 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.283 AC: 43000 AN: 152106 Hom.: 6929 Cov.: 32 AF XY: 0.283 AC XY: 21044 AN XY: 74332

African (AFR) AF: 0.149 AC: 6204 AN: 41520

American (AMR) AF: 0.260 AC: 3979 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3466

East Asian (EAS) AF: 0.114 AC: 594 AN: 5190

South Asian (SAS) AF: 0.333 AC: 1603 AN: 4808

European-Finnish (FIN) AF: 0.385 AC: 4060 AN: 10540

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24413 AN: 67972

Other (OTH) AF: 0.304 AC: 641 AN: 2112

Alfa AF: 0.336 Hom.: 15695

Bravo AF: 0.264

Asia WGS AF: 0.200 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.74
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: rs3829849; hg19: chr9-129390800; COSMIC: COSV62738600;