rs6478750

Variant names:

• chr9-126646919-T-C
• rs6478750
• NM_001174147.2:c.326+31350T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-126646919-T-C
• chr9-126646919-T-G

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+31350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,108 control chromosomes in the GnomAD database, including 10,325 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 0.36 (10325 hom., cov: 32)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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: 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+31350T>C		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+31350T>C		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+31350T>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+31350T>C		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+31350T>C		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+31350T>C		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54829 AN: 151990 Hom.: 10311 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.361 AC: 54864 AN: 152108 Hom.: 10325 Cov.: 32 AF XY: 0.354 AC XY: 26344 AN XY: 74358

African (AFR) AF: 0.382 AC: 15830 AN: 41494

American (AMR) AF: 0.312 AC: 4765 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.0835 AC: 433 AN: 5188

South Asian (SAS) AF: 0.324 AC: 1558 AN: 4802

European-Finnish (FIN) AF: 0.276 AC: 2925 AN: 10588

Middle Eastern (MID) AF: 0.510 AC: 148 AN: 290

European-Non Finnish (NFE) AF: 0.395 AC: 26837 AN: 67966

Other (OTH) AF: 0.360 AC: 758 AN: 2108

Alfa AF: 0.384 Hom.: 18400

Bravo AF: 0.360

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.59
PhyloP100		-0.086
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: rs6478750; hg19: chr9-129409198;