NM_001174147.2:c.*2184A>G

Variant names:

• chr9-126698635-A-G
• rs10733682
• NM_001174147.2:c.*2184A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174147.2(LMX1B):​c.*2184A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,168 control chromosomes in the GnomAD database, including 23,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23756 hom., cov: 32)
  • Exomes 𝑓: 0.48 (19 hom.)
• Consequence: LMX1B NM_001174147.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.321
• Publications: 91 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=-0.62).
• BP6: Variant 9-126698635-A-G is Benign according to our data. Variant chr9-126698635-A-G is described in ClinVar as Benign. ClinVar VariationId is 364952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.*2184A>G		3_prime_UTR	Exon 8 of 8	NP_001167618.1
	LMX1B	NM_001174146.2		c.*2184A>G		3_prime_UTR	Exon 8 of 8	NP_001167617.1
	LMX1B	NM_002316.4		c.*2184A>G		3_prime_UTR	Exon 8 of 8	NP_002307.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.*2184A>G		3_prime_UTR	Exon 8 of 8	ENSP00000362573.3
	LMX1B	ENST00000355497.10	TSL:1	c.*2184A>G		3_prime_UTR	Exon 8 of 8	ENSP00000347684.5
	LMX1B	ENST00000526117.6	TSL:1	c.*2184A>G		3_prime_UTR	Exon 8 of 8	ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82837 AN: 151868 Hom.: 23704 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.478 AC: 87 AN: 182 Hom.: 19 Cov.: 0 AF XY: 0.492 AC XY: 62 AN XY: 126

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.450 AC: 9 AN: 20

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.484 AC: 62 AN: 128

Other (OTH) AF: 0.500 AC: 7 AN: 14

GnomAD4 genome AF: 0.546 AC: 82949 AN: 151986 Hom.: 23756 Cov.: 32 AF XY: 0.538 AC XY: 39954 AN XY: 74286

African (AFR) AF: 0.718 AC: 29743 AN: 41432

American (AMR) AF: 0.413 AC: 6312 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1296 AN: 5166

South Asian (SAS) AF: 0.436 AC: 2098 AN: 4816

European-Finnish (FIN) AF: 0.461 AC: 4862 AN: 10548

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35042 AN: 67962

Other (OTH) AF: 0.536 AC: 1131 AN: 2110

Alfa AF: 0.516 Hom.: 70491

Bravo AF: 0.548

Asia WGS AF: 0.413 AC: 1439 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Nail-patella syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10733682; hg19: chr9-129460914;