9-126695813-G-T

Variant names:

Variant summary

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

The NM_001174147.2(LMX1B):c.887-26G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,610,684 control chromosomes in the GnomAD database, including 19,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4105 hom., cov: 31)

Exomes 𝑓: 0.13 ( 15567 hom. )

Consequence

LMX1B
NM_001174147.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.35

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=-0.94).

BP6

Variant 9-126695813-G-T is Benign according to our data. Variant chr9-126695813-G-T is described in ClinVar as [Benign]. Clinvar id is 1281138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2 link	c.887-26G>T	intron_variant	Intron 6 of 7	ENST00000373474.9	NP_001167618.1	O60663-1Q6ISE0
LMX1B	NM_001174146.2 link	c.920-26G>T	intron_variant	Intron 6 of 7		NP_001167617.1	B7ZLH2
LMX1B	NM_002316.4 link	c.887-26G>T	intron_variant	Intron 6 of 7		NP_002307.2	O60663-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMX1B	ENST00000373474.9 link	c.887-26G>T	intron_variant	Intron 6 of 7	1	NM_001174147.2	ENSP00000362573.3	O60663-1
LMX1B	ENST00000355497.10 link	c.920-26G>T	intron_variant	Intron 6 of 7	1		ENSP00000347684.5	O60663-3
LMX1B	ENST00000526117.6 link	c.887-26G>T	intron_variant	Intron 6 of 7	1		ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30392

AN:

151666

Hom.:

4086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.170

AC:

41663

AN:

245298

Hom.:

4707

AF XY:

0.157

AC XY:

20939

AN XY:

133240

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.0806

Gnomad EAS exome

AF:

0.369

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.133

AC:

193527

AN:

1458898

Hom.:

15567

Cov.:

AF XY:

0.130

AC XY:

94283

AN XY:

725754

show subpopulations

Gnomad4 AFR exome

AF:

0.373

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.0802

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.201

AC:

30450

AN:

151786

Hom.:

4105

Cov.:

AF XY:

0.201

AC XY:

14936

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.0741

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.144

Hom.:

888

Bravo

AF:

0.216

Asia WGS

AF:

0.197

AC:

686

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

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 28% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.15

DANN

Benign

0.48

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

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