NM_001174147.2:c.441A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001174147.2(LMX1B):c.441A>G(p.Glu147Glu) 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

Publications

22 publications found

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 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

LMX1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 258625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2 link	c.441A>G	p.Glu147Glu	synonymous_variant	Exon 3 of 8	ENST00000373474.9	NP_001167618.1	O60663-1Q6ISE0
LMX1B	NM_001174146.2 link	c.441A>G	p.Glu147Glu	synonymous_variant	Exon 3 of 8		NP_001167617.1	B7ZLH2
LMX1B	NM_002316.4 link	c.441A>G	p.Glu147Glu	synonymous_variant	Exon 3 of 8		NP_002307.2	O60663-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMX1B	ENST00000373474.9 link	c.441A>G	p.Glu147Glu	synonymous_variant	Exon 3 of 8	1	NM_001174147.2	ENSP00000362573.3	O60663-1
LMX1B	ENST00000355497.10 link	c.441A>G	p.Glu147Glu	synonymous_variant	Exon 3 of 8	1		ENSP00000347684.5	O60663-3
LMX1B	ENST00000526117.6 link	c.441A>G	p.Glu147Glu	synonymous_variant	Exon 3 of 8	1		ENSP00000436930.1	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

GnomAD2 exomes

AF:

0.444

AC:

111126

AN:

250096

AF XY:

0.442

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 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

African (AFR)

AF:

0.527

AC:

17626

AN:

33476

American (AMR)

AF:

0.449

AC:

20023

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

11571

AN:

26128

East Asian (EAS)

AF:

0.529

AC:

21002

AN:

39688

South Asian (SAS)

AF:

0.434

AC:

37463

AN:

86240

European-Finnish (FIN)

AF:

0.389

AC:

20794

AN:

53388

Middle Eastern (MID)

AF:

0.458

AC:

2641

AN:

5766

European-Non Finnish (NFE)

AF:

0.421

AC:

467603

AN:

1111776

Other (OTH)

AF:

0.438

AC:

26441

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

22324

44648

66973

89297

111621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14450

28900

43350

57800

72250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.456

AC:

69343

AN:

152102

Hom.:

16111

Cov.:

AF XY:

0.454

AC XY:

33724

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.524

AC:

21736

AN:

41512

American (AMR)

AF:

0.442

AC:

6764

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

1534

AN:

3466

East Asian (EAS)

AF:

0.541

AC:

2786

AN:

5146

South Asian (SAS)

AF:

0.423

AC:

2044

AN:

4830

European-Finnish (FIN)

AF:

0.382

AC:

4046

AN:

10590

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.426

AC:

28965

AN:

67950

Other (OTH)

AF:

0.445

AC:

941

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1981

3961

5942

7922

9903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.436

Hom.:

47191

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Nail-patella syndrome

Benign:2Other:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nail-patella-like renal disease

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.2

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over