rs112173596

Variant names:

• chr9-126693123-C-T
• rs112173596
• NM_001174147.2:c.560-19C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nail-patella syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• nail-patella-like renal disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 258628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1054 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174147.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.560-19C>T		intron	N/A	NP_001167618.1
	LMX1B	NM_001174146.2		c.560-19C>T		intron	N/A	NP_001167617.1
	LMX1B	NM_002316.4		c.560-19C>T		intron	N/A	NP_002307.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.560-19C>T		intron	N/A	ENSP00000362573.3
	LMX1B	ENST00000355497.10	TSL:1	c.560-19C>T		intron	N/A	ENSP00000347684.5
	LMX1B	ENST00000526117.6	TSL:1	c.560-19C>T		intron	N/A	ENSP00000436930.1

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

GnomAD2 exomes AF: 0.00356 AC: 578 AN: 162334 AF XY: 0.00314

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 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

African (AFR) AF: 0.0157 AC: 500 AN: 31850

American (AMR) AF: 0.00248 AC: 90 AN: 36352

Ashkenazi Jewish (ASJ) AF: 0.00722 AC: 182 AN: 25196

East Asian (EAS) AF: 0.0000276 AC: 1 AN: 36168

South Asian (SAS) AF: 0.00273 AC: 217 AN: 79554

European-Finnish (FIN) AF: 0.00192 AC: 95 AN: 49426

Middle Eastern (MID) AF: 0.00736 AC: 35 AN: 4756

European-Non Finnish (NFE) AF: 0.00242 AC: 2616 AN: 1081148

Other (OTH) AF: 0.00427 AC: 248 AN: 58086

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

African (AFR) AF: 0.0162 AC: 674 AN: 41576

American (AMR) AF: 0.00438 AC: 67 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4824

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 68026

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00600 Hom.: 1

Bravo AF: 0.00721

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.75
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112173596; hg19: chr9-129455402;