chr9-126644365-T-C

Variant names:

• chr9-126644365-T-C
• rs7858338
• NM_001174147.2:c.326+28796T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174147.2(LMX1B):​c.326+28796T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,056 control chromosomes in the GnomAD database, including 4,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4716 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+28796T>C		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+28796T>C		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+28796T>C		intron_variant	Intron 2 of 7		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+28796T>C		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+28796T>C		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+28796T>C		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36877 AN: 151938 Hom.: 4717 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36889 AN: 152056 Hom.: 4716 Cov.: 32 AF XY: 0.242 AC XY: 17948 AN XY: 74312

African (AFR) AF: 0.235 AC: 9733 AN: 41490

American (AMR) AF: 0.175 AC: 2671 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.00986 AC: 51 AN: 5172

South Asian (SAS) AF: 0.199 AC: 959 AN: 4810

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10564

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.265 AC: 17982 AN: 67956

Other (OTH) AF: 0.216 AC: 455 AN: 2108

Alfa AF: 0.246 Hom.: 12993

Bravo AF: 0.228

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.73
PhyloP100		-0.079
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: rs7858338; hg19: chr9-129406644;