1-165206278-A-G

Position:

• chr1-165206278-A-G

Variant summary

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

The NM_177398.4(LMX1A):​c.818-244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,094 control chromosomes in the GnomAD database, including 4,389 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 0.21 (4389 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1A	NM_177398.4	c.818-244T>C		intron_variant		ENST00000342310.7
LMX1A-AS2	XR_922234.2	n.366+508A>G		intron_variant, non_coding_transcript_variant
LMX1A	NM_001174069.2	c.818-244T>C		intron_variant
LMX1A	XM_011509538.4	c.578-244T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1A	ENST00000342310.7	c.818-244T>C		intron_variant		2	NM_177398.4	P1
LMX1A	ENST00000367893.4	c.818-244T>C		intron_variant		1		P1
LMX1A	ENST00000489443.2	n.452-244T>C		intron_variant, non_coding_transcript_variant		1
LMX1A	ENST00000294816.6	c.818-244T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32000 AN: 151976 Hom.: 4385 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.210 AC: 32014 AN: 152094 Hom.: 4389 Cov.: 32 AF XY: 0.220 AC XY: 16363 AN XY: 74326

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.218

Alfa AF: 0.237 Hom.: 2702

Bravo AF: 0.208

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.50

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: rs1354510; hg19: chr1-165175515;