9-126690950-A-G

Position:

chr9-126690950-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001174147.2(LMX1B):c.441A>G(p.Glu147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,590 control chromosomes in the GnomAD database, including 151,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16111 hom., cov: 33)

Exomes 𝑓: 0.43 ( 135024 hom. )

Consequence

LMX1B
NM_001174147.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: 1.17

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 9-126690950-A-G is Benign according to our data. Variant chr9-126690950-A-G is described in ClinVar as [Benign]. Clinvar id is 258625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-126690950-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LMX1B	NM_001174147.2 linkuse as main transcript	c.441A>G	p.Glu147=	synonymous_variant	3/8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2 linkuse as main transcript	c.441A>G	p.Glu147=	synonymous_variant	3/8		NP_001167617.1
LMX1B	NM_002316.4 linkuse as main transcript	c.441A>G	p.Glu147=	synonymous_variant	3/8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9 linkuse as main transcript	c.441A>G	p.Glu147=	synonymous_variant	3/8	1	NM_001174147.2	ENSP00000362573	P4	O60663-1
LMX1B	ENST00000355497.10 linkuse as main transcript	c.441A>G	p.Glu147=	synonymous_variant	3/8	1		ENSP00000347684		O60663-3
LMX1B	ENST00000526117.6 linkuse as main transcript	c.441A>G	p.Glu147=	synonymous_variant	3/8	1		ENSP00000436930	A1	O60663-2

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69282

AN:

151984

Hom.:

16091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.444

AC:

111126

AN:

250096

Hom.:

24918

AF XY:

0.442

AC XY:

59722

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.556

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.428

AC:

625164

AN:

1461488

Hom.:

135024

Cov.:

AF XY:

0.428

AC XY:

310994

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.527

Gnomad4 AMR exome

AF:

0.449

Gnomad4 ASJ exome

AF:

0.443

Gnomad4 EAS exome

AF:

0.529

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.438

GnomAD4 genome

AF:

0.456

AC:

69343

AN:

152102

Hom.:

16111

Cov.:

AF XY:

0.454

AC XY:

33724

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.524

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.423

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.431

Hom.:

28506

Bravo

AF:

0.464

Asia WGS

AF:

0.452

AC:

1572

AN:

3478

EpiCase

AF:

0.425

EpiControl

AF:

0.435

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 55. Only high quality variants are reported. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nail-patella syndrome

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 06-18-2018 by Lab or GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Nail-patella-like renal disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over