chr9-126615117-A-G

Position:

• chr9-126615117-A-G

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.140-266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,852 control chromosomes in the GnomAD database, including 5,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5161 hom., cov: 31)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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=-0.83).
• BP6: Variant 9-126615117-A-G is Benign according to our data. Variant chr9-126615117-A-G is described in ClinVar as [Benign]. Clinvar id is 1262332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.140-266A>G		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.140-266A>G		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.140-266A>G		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.140-266A>G		intron_variant		1	NM_001174147.2	ENSP00000362573	P4
LMX1B	ENST00000355497.10	c.140-266A>G		intron_variant		1		ENSP00000347684
LMX1B	ENST00000526117.6	c.140-266A>G		intron_variant		1		ENSP00000436930	A1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38562 AN: 151734 Hom.: 5163 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.254 AC: 38571 AN: 151852 Hom.: 5161 Cov.: 31 AF XY: 0.247 AC XY: 18351 AN XY: 74220

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.267

Alfa AF: 0.266 Hom.: 994

Bravo AF: 0.257

Asia WGS AF: 0.120 AC: 418 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

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.47

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: rs2235057; hg19: chr9-129377396;