rs7858338

Positions:

• chr9-126644365-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.326+28796T>C		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.326+28796T>C		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.326+28796T>C		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.326+28796T>C		intron_variant		1	NM_001174147.2	ENSP00000362573	P4
LMX1B	ENST00000355497.10	c.326+28796T>C		intron_variant		1		ENSP00000347684
LMX1B	ENST00000526117.6	c.326+28796T>C		intron_variant		1		ENSP00000436930	A1

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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.00986

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.216

Alfa AF: 0.247 Hom.: 8068

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7858338; hg19: chr9-129406644;