rs1343548

Positions:

• chr1-165245869-G-A
• chr1-165245869-G-T

Variant summary

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

The NM_177398.4(LMX1A):​c.496+3539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,484 control chromosomes in the GnomAD database, including 29,332 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 0.62 (29332 hom., cov: 29)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1A	NM_177398.4	c.496+3539C>T		intron_variant		ENST00000342310.7
LMX1A	NM_001174069.2	c.496+3539C>T		intron_variant
LMX1A	XM_011509538.4	c.256+3539C>T		intron_variant
LMX1A	XM_011509540.3	c.496+3539C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1A	ENST00000342310.7	c.496+3539C>T		intron_variant		2	NM_177398.4	P1
LMX1A	ENST00000367893.4	c.496+3539C>T		intron_variant		1		P1
LMX1A	ENST00000294816.6	c.496+3539C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93240 AN: 151366 Hom.: 29323 Cov.: 29

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.616 AC: 93281 AN: 151484 Hom.: 29332 Cov.: 29 AF XY: 0.617 AC XY: 45666 AN XY: 73958

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.619

Alfa AF: 0.647 Hom.: 15181

Bravo AF: 0.605

Asia WGS AF: 0.634 AC: 2205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.77

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: rs1343548; hg19: chr1-165215106;