9-126666398-A-G

Position:

• chr9-126666398-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174147.2(LMX1B):​c.327-24438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,024 control chromosomes in the GnomAD database, including 14,934 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 0.44 (14934 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1B	NM_001174147.2	c.327-24438A>G		intron_variant		ENST00000373474.9
LMX1B	NM_001174146.2	c.327-24438A>G		intron_variant
LMX1B	NM_002316.4	c.327-24438A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1B	ENST00000373474.9	c.327-24438A>G		intron_variant		1	NM_001174147.2	P4
LMX1B	ENST00000355497.10	c.327-24438A>G		intron_variant		1
LMX1B	ENST00000526117.6	c.327-24438A>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66893 AN: 151906 Hom.: 14916 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.440 AC: 66955 AN: 152024 Hom.: 14934 Cov.: 32 AF XY: 0.440 AC XY: 32687 AN XY: 74314

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.436

Alfa AF: 0.408 Hom.: 18070

Bravo AF: 0.445

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs4322101; hg19: chr9-129428677; COSMIC: COSV62738664;