rs2277158

Variant names:

• chr9-126690950-A-G
• rs2277158
• NM_001174147.2:c.441A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001174147.2(LMX1B):​c.441A>G​(p.Glu147Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,590 control chromosomes in the GnomAD database, including 151,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16111 hom., cov: 33)
  • Exomes 𝑓: 0.43 (135024 hom.)
• Consequence: LMX1B NM_001174147.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10 O:1
• Conservation: PhyloP100: 1.17
• Publications: 22 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• nail-patella-like renal disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 9-126690950-A-G is Benign according to our data. Variant chr9-126690950-A-G is described in ClinVar as Benign. ClinVar VariationId is 258625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.441A>G	p.Glu147Glu	synonymous	Exon 3 of 8	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.441A>G	p.Glu147Glu	synonymous	Exon 3 of 8	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.441A>G	p.Glu147Glu	synonymous	Exon 3 of 8	NP_002307.2	O60663-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.441A>G	p.Glu147Glu	synonymous	Exon 3 of 8	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.441A>G	p.Glu147Glu	synonymous	Exon 3 of 8	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.441A>G	p.Glu147Glu	synonymous	Exon 3 of 8	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69282 AN: 151984 Hom.: 16091 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.450

GnomAD2 exomes AF: 0.444 AC: 111126 AN: 250096 AF XY: 0.442

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.556

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.427

GnomAD4 exome AF: 0.428 AC: 625164 AN: 1461488 Hom.: 135024 Cov.: 56 AF XY: 0.428 AC XY: 310994 AN XY: 727038

African (AFR) AF: 0.527 AC: 17626 AN: 33476

American (AMR) AF: 0.449 AC: 20023 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11571 AN: 26128

East Asian (EAS) AF: 0.529 AC: 21002 AN: 39688

South Asian (SAS) AF: 0.434 AC: 37463 AN: 86240

European-Finnish (FIN) AF: 0.389 AC: 20794 AN: 53388

Middle Eastern (MID) AF: 0.458 AC: 2641 AN: 5766

European-Non Finnish (NFE) AF: 0.421 AC: 467603 AN: 1111776

Other (OTH) AF: 0.438 AC: 26441 AN: 60382

GnomAD4 genome AF: 0.456 AC: 69343 AN: 152102 Hom.: 16111 Cov.: 33 AF XY: 0.454 AC XY: 33724 AN XY: 74346

African (AFR) AF: 0.524 AC: 21736 AN: 41512

American (AMR) AF: 0.442 AC: 6764 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1534 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2786 AN: 5146

South Asian (SAS) AF: 0.423 AC: 2044 AN: 4830

European-Finnish (FIN) AF: 0.382 AC: 4046 AN: 10590

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28965 AN: 67950

Other (OTH) AF: 0.445 AC: 941 AN: 2114

Alfa AF: 0.436 Hom.: 47191

Bravo AF: 0.464

Asia WGS AF: 0.452 AC: 1572 AN: 3478

EpiCase AF: 0.425

EpiControl AF: 0.435

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Nail-patella syndrome (3)
-	-	1	Nail-patella-like renal disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		1.2
Mutation Taster		=98/2	polymorphism (auto)

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: rs2277158; hg19: chr9-129453229; COSMIC: COSV62738692;