NM_001174147.2:c.*2184A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174147.2(LMX1B):c.*2184A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,168 control chromosomes in the GnomAD database, including 23,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23756 hom., cov: 32)

Exomes 𝑓: 0.48 ( 19 hom. )

Consequence

LMX1B
NM_001174147.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.321

Publications

91 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 9-126698635-A-G is Benign according to our data. Variant chr9-126698635-A-G is described in ClinVar as Benign. ClinVar VariationId is 364952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2 link	c.*2184A>G	3_prime_UTR_variant	Exon 8 of 8	ENST00000373474.9	NP_001167618.1	O60663-1Q6ISE0
LMX1B	NM_001174146.2 link	c.*2184A>G	3_prime_UTR_variant	Exon 8 of 8		NP_001167617.1	B7ZLH2
LMX1B	NM_002316.4 link	c.*2184A>G	3_prime_UTR_variant	Exon 8 of 8		NP_002307.2	O60663-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMX1B	ENST00000373474.9 link	c.*2184A>G	3_prime_UTR_variant	Exon 8 of 8	1	NM_001174147.2	ENSP00000362573.3	O60663-1
LMX1B	ENST00000355497.10 link	c.*2184A>G	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000347684.5	O60663-3
LMX1B	ENST00000526117.6 link	c.*2184A>G	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82837

AN:

151868

Hom.:

23704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.478

AC:

AN:

182

Hom.:

Cov.:

AF XY:

0.492

AC XY:

AN XY:

126

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.450

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.484

AC:

AN:

128

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.546

AC:

82949

AN:

151986

Hom.:

23756

Cov.:

AF XY:

0.538

AC XY:

39954

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.718

AC:

29743

AN:

41432

American (AMR)

AF:

0.413

AC:

6312

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1804

AN:

3472

East Asian (EAS)

AF:

0.251

AC:

1296

AN:

5166

South Asian (SAS)

AF:

0.436

AC:

2098

AN:

4816

European-Finnish (FIN)

AF:

0.461

AC:

4862

AN:

10548

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35042

AN:

67962

Other (OTH)

AF:

0.536

AC:

1131

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1845

3690

5534

7379

9224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.516

Hom.:

70491

Bravo

AF:

0.548

Asia WGS

AF:

0.413

AC:

1439

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nail-patella syndrome

Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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