rs4657411

Variant names:

• chr1-165204312-G-A
• rs4657411
• NM_177398.4:c.989-272C>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.989-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,032 control chromosomes in the GnomAD database, including 19,099 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 0.48 (19099 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.989-272C>T		intron_variant	Intron 8 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.989-272C>T		intron_variant	Intron 8 of 8		NP_001167540.1
LMX1A	XM_011509538.4	c.749-272C>T		intron_variant	Intron 6 of 6		XP_011507840.1
LMX1A-AS2	XR_922234.2	n.101+165G>A		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.989-272C>T		intron_variant	Intron 8 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.989-272C>T		intron_variant	Intron 7 of 7	1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.623-272C>T		intron_variant	Intron 6 of 6	1
LMX1A	ENST00000294816.6	c.989-272C>T		intron_variant	Intron 8 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72408 AN: 151912 Hom.: 19095 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.476 AC: 72424 AN: 152032 Hom.: 19099 Cov.: 32 AF XY: 0.473 AC XY: 35129 AN XY: 74326

African (AFR) AF: 0.279 AC: 11563 AN: 41462

American (AMR) AF: 0.446 AC: 6819 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1597 AN: 3468

East Asian (EAS) AF: 0.170 AC: 877 AN: 5162

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4810

European-Finnish (FIN) AF: 0.610 AC: 6438 AN: 10562

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41319 AN: 67968

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.557 Hom.: 30070

Bravo AF: 0.455

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.89
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: rs4657411; hg19: chr1-165173549;