rs4657412

chr1-165207796-G-Achr1-165207796-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177398.4(LMX1A):c.817+267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,142 control chromosomes in the GnomAD database, including 47,781 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 0.78 (47781 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

Genes affected

LMX1A (HGNC:6653): (LIM homeobox transcription factor 1 alpha) This gene encodes a homeodomain and LIM-domain containing protein. The encoded protein is a transcription factor that acts as a positive regulator of insulin gene transcription. This gene also plays a role in the development of dopamine producing neurons during embryogenesis. Mutations in this gene are associated with an increased risk of developing Parkinson's disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

LMX1A-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1A	NM_177398.4	c.817+267C>T		intron_variant		ENST00000342310.7
LMX1A-AS2	XR_922234.2	n.433G>A		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1A	ENST00000342310.7	c.817+267C>T		intron_variant		2	NM_177398.4	P1
LMX1A	ENST00000367893.4	c.817+267C>T		intron_variant		1		P1
LMX1A	ENST00000489443.2	n.319-182C>T		intron_variant, non_coding_transcript_variant		1
LMX1A	ENST00000294816.6	c.817+267C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118900 AN: 152024 Hom.: 47734 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.782 AC: 119001 AN: 152142 Hom.: 47781 Cov.: 32 AF XY: 0.771 AC XY: 57382 AN XY: 74382

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.773

Alfa AF: 0.782 Hom.: 13889

Bravo AF: 0.785

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.064
Dann	Benign	0.49

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: rs4657412; hg19: chr1-165177033; COSMIC: COSV54230790; COSMIC: COSV54230790;