9-126651211-C-T

Position:

• chr9-126651211-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001174147.2(LMX1B):​c.326+35642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,588 control chromosomes in the GnomAD database, including 21,220 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 0.52 (21220 hom., cov: 30)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1B	NM_001174147.2	c.326+35642C>T		intron_variant		ENST00000373474.9
LMX1B	NM_001174146.2	c.326+35642C>T		intron_variant
LMX1B	NM_002316.4	c.326+35642C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+35642C>T		intron_variant		1	NM_001174147.2	P4
LMX1B	ENST00000355497.10	c.326+35642C>T		intron_variant		1
LMX1B	ENST00000526117.6	c.326+35642C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78339 AN: 151470 Hom.: 21186 Cov.: 30

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.517 AC: 78433 AN: 151588 Hom.: 21220 Cov.: 30 AF XY: 0.529 AC XY: 39159 AN XY: 74034

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.969

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.555

Alfa AF: 0.401 Hom.: 2144

Bravo AF: 0.528

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.82

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: rs944103; hg19: chr9-129413490;