rs112173596

Positions:

• chr9-126693123-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001174147.2(LMX1B):​c.560-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,554,862 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (7 hom., cov: 34)
  • Exomes 𝑓: 0.0028 (22 hom.)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.85

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=-0.87).
• BP6: Variant 9-126693123-C-T is Benign according to our data. Variant chr9-126693123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-126693123-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00692 (1054/152326) while in subpopulation AFR AF= 0.0162 (674/41576). AF 95% confidence interval is 0.0152. There are 7 homozygotes in gnomad4. There are 458 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1054 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1B	NM_001174147.2	c.560-19C>T		intron_variant		ENST00000373474.9
LMX1B	NM_001174146.2	c.560-19C>T		intron_variant
LMX1B	NM_002316.4	c.560-19C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1B	ENST00000373474.9	c.560-19C>T		intron_variant		1	NM_001174147.2	P4
LMX1B	ENST00000355497.10	c.560-19C>T		intron_variant		1
LMX1B	ENST00000526117.6	c.560-19C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1053 AN: 152208 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00356 AC: 578 AN: 162334 Hom.: 4 AF XY: 0.00314 AC XY: 271 AN XY: 86394

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.00575

Gnomad EAS exome AF: 0.0000840

Gnomad SAS exome AF: 0.00272

Gnomad FIN exome AF: 0.00241

Gnomad NFE exome AF: 0.00320

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00284 AC: 3984 AN: 1402536 Hom.: 22 Cov.: 32 AF XY: 0.00287 AC XY: 1989 AN XY: 692124

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00722

Gnomad4 EAS exome AF: 0.0000276

Gnomad4 SAS exome AF: 0.00273

Gnomad4 FIN exome AF: 0.00192

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.00692 AC: 1054 AN: 152326 Hom.: 7 Cov.: 34 AF XY: 0.00615 AC XY: 458 AN XY: 74476

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00332

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00596 Hom.: 0

Bravo AF: 0.00721

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs112173596; hg19: chr9-129455402;