chr9-126659744-G-A

Variant names:

• chr9-126659744-G-A
• rs10819194
• NM_001174147.2:c.327-31092G>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.327-31092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 150,220 control chromosomes in the GnomAD database, including 8,367 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 (8367 hom., cov: 33)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.327-31092G>A		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.327-31092G>A		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.327-31092G>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.327-31092G>A		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.327-31092G>A		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.327-31092G>A		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50366 AN: 150100 Hom.: 8366 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.335 AC: 50382 AN: 150220 Hom.: 8367 Cov.: 33 AF XY: 0.324 AC XY: 23846 AN XY: 73488

African (AFR) AF: 0.320 AC: 13117 AN: 40974

American (AMR) AF: 0.277 AC: 4199 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1275 AN: 3420

East Asian (EAS) AF: 0.148 AC: 756 AN: 5112

South Asian (SAS) AF: 0.243 AC: 1161 AN: 4768

European-Finnish (FIN) AF: 0.237 AC: 2486 AN: 10480

Middle Eastern (MID) AF: 0.357 AC: 100 AN: 280

European-Non Finnish (NFE) AF: 0.392 AC: 26286 AN: 67058

Other (OTH) AF: 0.338 AC: 706 AN: 2088

Alfa AF: 0.177 Hom.: 232

Asia WGS AF: 0.213 AC: 740 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.51
DANN	Benign	0.65
PhyloP100		0.80
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: rs10819194; hg19: chr9-129422023;