rs1395548

Positions:

• chr1-165344190-A-C
• chr1-165344190-A-G
• chr1-165344190-A-T

Variant summary

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

The NM_177398.4(LMX1A):​c.263+8886T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,154 control chromosomes in the GnomAD database, including 24,526 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 0.55 (24526 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.263+8886T>G		intron_variant		ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.263+8886T>G		intron_variant			NP_001167540.1
LMX1A	XM_011509540.3	c.263+8886T>G		intron_variant			XP_011507842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.263+8886T>G		intron_variant		2	NM_177398.4	ENSP00000340226	P1
LMX1A	ENST00000367893.4	c.263+8886T>G		intron_variant		1		ENSP00000356868	P1
LMX1A	ENST00000294816.6	c.263+8886T>G		intron_variant		2		ENSP00000294816	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84334 AN: 152036 Hom.: 24531 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.554 AC: 84352 AN: 152154 Hom.: 24526 Cov.: 32 AF XY: 0.559 AC XY: 41595 AN XY: 74388

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.564

Alfa AF: 0.605 Hom.: 57251

Bravo AF: 0.544

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.72

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: rs1395548; hg19: chr1-165313427;