rs10987417

Variant names:

• chr9-126700222-G-T
• rs10987417
• NM_001174147.2:c.*3771G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174147.2(LMX1B):​c.*3771G>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 0.43 in 152,018 control chromosomes in the GnomAD database, including 14,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14817 hom., cov: 31)
  • Exomes 𝑓: 0.44 (20 hom.)
• Consequence: LMX1B NM_001174147.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.42

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-126700222-G-T is Benign according to our data. Variant chr9-126700222-G-T is described in ClinVar as [Benign]. Clinvar id is 364979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.*3771G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.*3771G>T		3_prime_UTR_variant	Exon 8 of 8		NP_001167617.1
LMX1B	NM_002316.4	c.*3771G>T		3_prime_UTR_variant	Exon 8 of 8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.*3771G>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.*3771G>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.*3771G>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65302 AN: 151740 Hom.: 14810 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.438 AC: 70 AN: 160 Hom.: 20 Cov.: 0 AF XY: 0.441 AC XY: 52 AN XY: 118

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.430 AC: 65354 AN: 151858 Hom.: 14817 Cov.: 31 AF XY: 0.443 AC XY: 32884 AN XY: 74196

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.421

Alfa AF: 0.423 Hom.: 7473

Bravo AF: 0.426

Asia WGS AF: 0.681 AC: 2365 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10987417; hg19: chr9-129462501;