rs10760450

chr9-126697349-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001174147.2(LMX1B):c.*898C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,402 control chromosomes in the GnomAD database, including 1,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1900 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: LMX1B NM_001174147.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.351

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-126697349-C-T is Benign according to our data. Variant chr9-126697349-C-T is described in ClinVar as [Benign]. Clinvar id is 364914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1B	NM_001174147.2	c.*898C>T		3_prime_UTR_variant	8/8	ENST00000373474.9
LMX1B	NM_001174146.2	c.*898C>T		3_prime_UTR_variant	8/8
LMX1B	NM_002316.4	c.*898C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1B	ENST00000373474.9	c.*898C>T		3_prime_UTR_variant	8/8	1	NM_001174147.2	P4
LMX1B	ENST00000355497.10	c.*898C>T		3_prime_UTR_variant	8/8	1
LMX1B	ENST00000526117.6	c.*898C>T		3_prime_UTR_variant	8/8	1		A1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21058 AN: 152016 Hom.: 1902 Cov.: 32

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.123 AC: 33 AN: 268 Hom.: 3 Cov.: 0 AF XY: 0.110 AC XY: 24 AN XY: 218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.138 AC: 21051 AN: 152134 Hom.: 1900 Cov.: 32 AF XY: 0.134 AC XY: 9959 AN XY: 74364

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.129

Alfa AF: 0.187 Hom.: 3889

Bravo AF: 0.128

Asia WGS AF: 0.0500 AC: 172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.82
Cadd	Benign	8.3
Dann	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10760450; hg19: chr9-129459628;