9-126614797-C-T

Position:

• chr9-126614797-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001174147.2(LMX1B):​c.139+209C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,226 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.044 (214 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.456

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-126614797-C-T is Benign according to our data. Variant chr9-126614797-C-T is described in ClinVar as [Benign]. Clinvar id is 1230698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.139+209C>T		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.139+209C>T		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.139+209C>T		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.139+209C>T		intron_variant		1	NM_001174147.2	ENSP00000362573	P4
LMX1B	ENST00000355497.10	c.139+209C>T		intron_variant		1		ENSP00000347684
LMX1B	ENST00000526117.6	c.139+209C>T		intron_variant		1		ENSP00000436930	A1

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6634 AN: 152108 Hom.: 214 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0436 AC: 6635 AN: 152226 Hom.: 214 Cov.: 31 AF XY: 0.0435 AC XY: 3234 AN XY: 74416

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0595

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0625

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0464 Hom.: 106

Bravo AF: 0.0444

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2235055; hg19: chr9-129377076;