chr9-126697159-G-A

Variant names:

• chr9-126697159-G-A
• rs10987413
• NM_001174147.2:c.*708G>A

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.*708G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,478 control chromosomes in the GnomAD database, including 5,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5196 hom., cov: 32)
  • Exomes 𝑓: 0.24 (7 hom.)
• Consequence: LMX1B NM_001174147.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-126697159-G-A is Benign according to our data. Variant chr9-126697159-G-A is described in ClinVar as Benign. ClinVar VariationId is 364912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 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.*708G>A		3_prime_UTR	Exon 8 of 8	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.*708G>A		3_prime_UTR	Exon 8 of 8	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.*708G>A		3_prime_UTR	Exon 8 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.*708G>A		3_prime_UTR	Exon 8 of 8	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.*708G>A		3_prime_UTR	Exon 8 of 8	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.*708G>A		3_prime_UTR	Exon 8 of 8	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35777 AN: 152094 Hom.: 5194 Cov.: 32

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.241 AC: 64 AN: 266 Hom.: 7 Cov.: 0 AF XY: 0.216 AC XY: 38 AN XY: 176

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.200 AC: 2 AN: 10

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 3 AN: 6

European-Finnish (FIN) AF: 0.250 AC: 8 AN: 32

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.253 AC: 48 AN: 190

Other (OTH) AF: 0.150 AC: 3 AN: 20

GnomAD4 genome AF: 0.235 AC: 35772 AN: 152212 Hom.: 5196 Cov.: 32 AF XY: 0.233 AC XY: 17330 AN XY: 74412

African (AFR) AF: 0.0671 AC: 2787 AN: 41550

American (AMR) AF: 0.247 AC: 3781 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3468

East Asian (EAS) AF: 0.191 AC: 990 AN: 5176

South Asian (SAS) AF: 0.334 AC: 1609 AN: 4820

European-Finnish (FIN) AF: 0.241 AC: 2551 AN: 10604

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21758 AN: 67982

Other (OTH) AF: 0.275 AC: 582 AN: 2116

Alfa AF: 0.274 Hom.: 2173

Bravo AF: 0.223

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	1.8
DANN	Benign	0.45
PhyloP100		-0.69
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: rs10987413; hg19: chr9-129459438; COSMIC: COSV62738711; COSMIC: COSV62738711;