Variant rs10987413 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174147.2(LMX1B):c.*708G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,478 control chromosomes in the GnomAD database, including 5,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5196 hom., cov: 32)

Exomes 𝑓: 0.24 ( 7 hom. )

Consequence

LMX1B
NM_001174147.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.694

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-126697159-G-A is Benign according to our data. Variant chr9-126697159-G-A is described in ClinVar as [Benign]. Clinvar id is 364912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
LMX1B	NM_001174147.2 linkuse as main transcript	c.*708G>A	3_prime_UTR_variant	8/8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2 linkuse as main transcript	c.*708G>A	3_prime_UTR_variant	8/8		NP_001167617.1
LMX1B	NM_002316.4 linkuse as main transcript	c.*708G>A	3_prime_UTR_variant	8/8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9 linkuse as main transcript	c.*708G>A	3_prime_UTR_variant	8/8	1	NM_001174147.2	ENSP00000362573	P4	O60663-1
LMX1B	ENST00000355497.10 linkuse as main transcript	c.*708G>A	3_prime_UTR_variant	8/8	1		ENSP00000347684		O60663-3
LMX1B	ENST00000526117.6 linkuse as main transcript	c.*708G>A	3_prime_UTR_variant	8/8	1		ENSP00000436930	A1	O60663-2

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35777

AN:

152094

Hom.:

5194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.241

AC:

AN:

266

Hom.:

Cov.:

AF XY:

0.216

AC XY:

AN XY:

176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.235

AC:

35772

AN:

152212

Hom.:

5196

Cov.:

AF XY:

0.233

AC XY:

17330

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0671

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.279

Hom.:

1118

Bravo

AF:

0.223

Asia WGS

AF:

0.254

AC:

885

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Nail-patella syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

DANN

Benign

0.45

Splicing

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