rs6671290

Positions:

• chr1-165206270-T-C

Variant summary

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

The NM_177398.4(LMX1A):​c.818-236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 152,196 control chromosomes in the GnomAD database, including 393 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 0.065 (393 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.818-236A>G		intron_variant		ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.818-236A>G		intron_variant			NP_001167540.1
LMX1A	XM_011509538.4	c.578-236A>G		intron_variant			XP_011507840.1
LMX1A-AS2	XR_922234.2	n.366+500T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.818-236A>G		intron_variant		2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.818-236A>G		intron_variant		1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.452-236A>G		intron_variant		1
LMX1A	ENST00000294816.6	c.818-236A>G		intron_variant		2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9833 AN: 152078 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0759

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0647 AC: 9853 AN: 152196 Hom.: 393 Cov.: 32 AF XY: 0.0633 AC XY: 4712 AN XY: 74418

Gnomad4 AFR AF: 0.0970

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0759

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0532 Hom.: 209

Bravo AF: 0.0662

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
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: rs6671290; hg19: chr1-165175507;