rs1354510

Variant names:

• chr1-165206278-A-G
• rs1354510
• NM_177398.4:c.818-244T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-165206278-A-G
• chr1-165206278-A-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.818-244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,094 control chromosomes in the GnomAD database, including 4,389 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 0.21 (4389 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.818-244T>C		intron_variant	Intron 7 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.818-244T>C		intron_variant	Intron 7 of 8		NP_001167540.1
LMX1A	XM_011509538.4	c.578-244T>C		intron_variant	Intron 5 of 6		XP_011507840.1
LMX1A-AS2	XR_922234.2	n.366+508A>G		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.818-244T>C		intron_variant	Intron 7 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.818-244T>C		intron_variant	Intron 6 of 7	1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.452-244T>C		intron_variant	Intron 5 of 6	1
LMX1A	ENST00000294816.6	c.818-244T>C		intron_variant	Intron 7 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32000 AN: 151976 Hom.: 4385 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.210 AC: 32014 AN: 152094 Hom.: 4389 Cov.: 32 AF XY: 0.220 AC XY: 16363 AN XY: 74326

African (AFR) AF: 0.0610 AC: 2536 AN: 41546

American (AMR) AF: 0.323 AC: 4925 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1147 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2499 AN: 5144

South Asian (SAS) AF: 0.364 AC: 1752 AN: 4818

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10560

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15679 AN: 67972

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.235 Hom.: 3765

Bravo AF: 0.208

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-0.49
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: rs1354510; hg19: chr1-165175515;