1-165317042-A-G

Variant names:

• chr1-165317042-A-G
• rs2348250
• NM_177398.4:c.263+36034T>C

Variant summary

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

The NM_177398.4(LMX1A):​c.263+36034T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,208 control chromosomes in the GnomAD database, including 58,483 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 0.87 (58483 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.263+36034T>C		intron_variant	Intron 3 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.263+36034T>C		intron_variant	Intron 3 of 8		NP_001167540.1
LMX1A	XM_011509540.3	c.263+36034T>C		intron_variant	Intron 3 of 7		XP_011507842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.263+36034T>C		intron_variant	Intron 3 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.263+36034T>C		intron_variant	Intron 2 of 7	1		ENSP00000356868.4
LMX1A	ENST00000294816.6	c.263+36034T>C		intron_variant	Intron 3 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132784 AN: 152090 Hom.: 58441 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.914

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.873 AC: 132879 AN: 152208 Hom.: 58483 Cov.: 32 AF XY: 0.871 AC XY: 64837 AN XY: 74416

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.868

Alfa AF: 0.890 Hom.: 10231

Bravo AF: 0.864

Asia WGS AF: 0.868 AC: 3020 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	3.1
DANN	Benign	0.82

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: rs2348250; hg19: chr1-165286279;