chr9-126652659-G-A

Position:

• chr9-126652659-G-A

Variant summary

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

The NM_001174147.2(LMX1B):​c.326+37090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,198 control chromosomes in the GnomAD database, including 6,136 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 0.25 (6136 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+37090G>A		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+37090G>A		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.326+37090G>A		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+37090G>A		intron_variant		1	NM_001174147.2	ENSP00000362573	P4
LMX1B	ENST00000355497.10	c.326+37090G>A		intron_variant		1		ENSP00000347684
LMX1B	ENST00000526117.6	c.326+37090G>A		intron_variant		1		ENSP00000436930	A1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38096 AN: 152080 Hom.: 6112 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.251 AC: 38156 AN: 152198 Hom.: 6136 Cov.: 32 AF XY: 0.243 AC XY: 18062 AN XY: 74442

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.200

Alfa AF: 0.232 Hom.: 954

Bravo AF: 0.258

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
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: rs7854658; hg19: chr9-129414938;