NM_177398.4:c.818-236A>G

Variant names:

• chr1-165206270-T-C
• rs6671290
• NM_177398.4:c.818-236A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.89).
• 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 rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.818-236A>G		intron_variant	Intron 7 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.818-236A>G		intron_variant	Intron 7 of 8		NP_001167540.1
LMX1A	XM_011509538.4	c.578-236A>G		intron_variant	Intron 5 of 6		XP_011507840.1
LMX1A-AS2	XR_922234.2	n.366+500T>C		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.818-236A>G		intron_variant	Intron 7 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.818-236A>G		intron_variant	Intron 6 of 7	1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.452-236A>G		intron_variant	Intron 5 of 6	1
LMX1A	ENST00000294816.6	c.818-236A>G		intron_variant	Intron 7 of 8	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

African (AFR) AF: 0.0970 AC: 4026 AN: 41494

American (AMR) AF: 0.0424 AC: 649 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0759 AC: 263 AN: 3466

East Asian (EAS) AF: 0.111 AC: 575 AN: 5176

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4822

European-Finnish (FIN) AF: 0.0472 AC: 501 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0513 AC: 3492 AN: 68016

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0545 Hom.: 268

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
PhyloP100		0.073
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: rs6671290; hg19: chr1-165175507;