1-165207796-G-A

Variant names:

• chr1-165207796-G-A
• rs4657412
• NM_177398.4:c.817+267C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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:40343): (LMX1A antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177398.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	NM_177398.4	MANE Select	c.817+267C>T		intron	N/A	NP_796372.1
	LMX1A	NM_001174069.2		c.817+267C>T		intron	N/A	NP_001167540.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	ENST00000342310.7	TSL:2 MANE Select	c.817+267C>T		intron	N/A	ENSP00000340226.3
	LMX1A	ENST00000367893.4	TSL:1	c.817+267C>T		intron	N/A	ENSP00000356868.4
	LMX1A	ENST00000489443.2	TSL:1	n.319-182C>T		intron	N/A

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

African (AFR) AF: 0.935 AC: 38833 AN: 41544

American (AMR) AF: 0.676 AC: 10324 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2323 AN: 3472

East Asian (EAS) AF: 0.385 AC: 1988 AN: 5158

South Asian (SAS) AF: 0.593 AC: 2856 AN: 4818

European-Finnish (FIN) AF: 0.727 AC: 7698 AN: 10584

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.769 AC: 52279 AN: 67980

Other (OTH) AF: 0.773 AC: 1632 AN: 2110

Alfa AF: 0.785 Hom.: 17852

Bravo AF: 0.785

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.064
DANN	Benign	0.49
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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