rs10819190

Variant names:

• chr9-126646234-G-A
• rs10819190
• NM_001174147.2:c.326+30665G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-126646234-G-A
• chr9-126646234-G-C
• chr9-126646234-G-T

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+30665G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,914 control chromosomes in the GnomAD database, including 9,274 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 0.33 (9274 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+30665G>A		intron_variant	Intron 2 of 7	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+30665G>A		intron_variant	Intron 2 of 7		NP_001167617.1
LMX1B	NM_002316.4	c.326+30665G>A		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+30665G>A		intron_variant	Intron 2 of 7	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.326+30665G>A		intron_variant	Intron 2 of 7	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.326+30665G>A		intron_variant	Intron 2 of 7	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50506 AN: 151796 Hom.: 9272 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.333 AC: 50520 AN: 151914 Hom.: 9274 Cov.: 31 AF XY: 0.336 AC XY: 24947 AN XY: 74206

African (AFR) AF: 0.176 AC: 7277 AN: 41436

American (AMR) AF: 0.365 AC: 5579 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1351 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2848 AN: 5138

South Asian (SAS) AF: 0.384 AC: 1843 AN: 4800

European-Finnish (FIN) AF: 0.410 AC: 4320 AN: 10546

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26299 AN: 67932

Other (OTH) AF: 0.364 AC: 767 AN: 2108

Alfa AF: 0.375 Hom.: 19101

Bravo AF: 0.324

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.39
PhyloP100		-0.0040
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: rs10819190; hg19: chr9-129408513; COSMIC: COSV62738619; COSMIC: COSV62738619;