rs3737048

Variant names:

• chr9-126695813-G-T
• rs3737048
• NM_001174147.2:c.887-26G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-126695813-G-T
• chr9-126695813-G-A
• chr9-126695813-G-C

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.887-26G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,610,684 control chromosomes in the GnomAD database, including 19,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4105 hom., cov: 31)
  • Exomes 𝑓: 0.13 (15567 hom.)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.35
• Publications: 7 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=-0.94).
• BP6: Variant 9-126695813-G-T is Benign according to our data. Variant chr9-126695813-G-T is described in ClinVar as Benign. ClinVar VariationId is 1281138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 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.887-26G>T		intron	N/A	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.920-26G>T		intron	N/A	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.887-26G>T		intron	N/A	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.887-26G>T		intron	N/A	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.920-26G>T		intron	N/A	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.887-26G>T		intron	N/A	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30392 AN: 151666 Hom.: 4086 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.170 AC: 41663 AN: 245298 AF XY: 0.157

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.0806

Gnomad EAS exome AF: 0.369

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.133 AC: 193527 AN: 1458898 Hom.: 15567 Cov.: 33 AF XY: 0.130 AC XY: 94283 AN XY: 725754

African (AFR) AF: 0.373 AC: 12463 AN: 33410

American (AMR) AF: 0.239 AC: 10642 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 2084 AN: 25990

East Asian (EAS) AF: 0.329 AC: 13060 AN: 39664

South Asian (SAS) AF: 0.101 AC: 8720 AN: 86112

European-Finnish (FIN) AF: 0.149 AC: 7874 AN: 52932

Middle Eastern (MID) AF: 0.104 AC: 538 AN: 5168

European-Non Finnish (NFE) AF: 0.117 AC: 129528 AN: 1110802

Other (OTH) AF: 0.143 AC: 8618 AN: 60236

GnomAD4 genome AF: 0.201 AC: 30450 AN: 151786 Hom.: 4105 Cov.: 31 AF XY: 0.201 AC XY: 14936 AN XY: 74150

African (AFR) AF: 0.366 AC: 15114 AN: 41294

American (AMR) AF: 0.196 AC: 2989 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1800 AN: 5126

South Asian (SAS) AF: 0.105 AC: 504 AN: 4818

European-Finnish (FIN) AF: 0.150 AC: 1584 AN: 10586

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7724 AN: 67900

Other (OTH) AF: 0.158 AC: 334 AN: 2110

Alfa AF: 0.147 Hom.: 1370

Bravo AF: 0.216

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.48
PhyloP100		-3.4
Mutation Taster		=100/0	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: rs3737048; hg19: chr9-129458092; COSMIC: COSV62740845;