rs76196383

Positions:

• chr9-126691088-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174147.2(LMX1B):​c.559+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,577,490 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (187 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (160 hom.)
• Consequence: LMX1B NM_001174147.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.685

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-126691088-G-A is Benign according to our data. Variant chr9-126691088-G-A is described in ClinVar as [Benign]. Clinvar id is 258627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-126691088-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.559+20G>A		intron_variant		ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.559+20G>A		intron_variant			NP_001167617.1
LMX1B	NM_002316.4	c.559+20G>A		intron_variant			NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.559+20G>A		intron_variant		1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.559+20G>A		intron_variant		1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.559+20G>A		intron_variant		1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4019 AN: 152028 Hom.: 186 Cov.: 33

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00657 AC: 1382 AN: 210276 Hom.: 58 AF XY: 0.00464 AC XY: 531 AN XY: 114550

Gnomad AFR exome AF: 0.0972

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000145

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.00481

GnomAD4 exome AF: 0.00282 AC: 4022 AN: 1425346 Hom.: 160 Cov.: 31 AF XY: 0.00233 AC XY: 1652 AN XY: 708722

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00468

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000167

Gnomad4 FIN exome AF: 0.0000386

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.0266 AC: 4041 AN: 152144 Hom.: 187 Cov.: 33 AF XY: 0.0257 AC XY: 1911 AN XY: 74388

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0124 Hom.: 16

Bravo AF: 0.0307

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76196383; hg19: chr9-129453367;