rs1343548

Variant names:

• chr1-165245869-G-A
• rs1343548
• NM_177398.4:c.496+3539C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-165245869-G-A
• chr1-165245869-G-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.496+3539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,484 control chromosomes in the GnomAD database, including 29,332 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 0.62 (29332 hom., cov: 29)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• 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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss 7

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Mobius syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	NM_177398.4	MANE Select	c.496+3539C>T		intron	N/A	NP_796372.1	Q8TE12-1
	LMX1A	NM_001174069.2		c.496+3539C>T		intron	N/A	NP_001167540.1	Q8TE12-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	ENST00000342310.7	TSL:2 MANE Select	c.496+3539C>T		intron	N/A	ENSP00000340226.3	Q8TE12-1
	LMX1A	ENST00000367893.4	TSL:1	c.496+3539C>T		intron	N/A	ENSP00000356868.4	Q8TE12-1
	LMX1A	ENST00000294816.6	TSL:2	c.496+3539C>T		intron	N/A	ENSP00000294816.2	Q8TE12-1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93240 AN: 151366 Hom.: 29323 Cov.: 29

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.616 AC: 93281 AN: 151484 Hom.: 29332 Cov.: 29 AF XY: 0.617 AC XY: 45666 AN XY: 73958

African (AFR) AF: 0.491 AC: 20244 AN: 41242

American (AMR) AF: 0.627 AC: 9531 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2281 AN: 3466

East Asian (EAS) AF: 0.714 AC: 3668 AN: 5140

South Asian (SAS) AF: 0.654 AC: 3121 AN: 4772

European-Finnish (FIN) AF: 0.673 AC: 7048 AN: 10468

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45247 AN: 67892

Other (OTH) AF: 0.619 AC: 1304 AN: 2108

Alfa AF: 0.648 Hom.: 16980

Bravo AF: 0.605

Asia WGS AF: 0.634 AC: 2205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.77
PhyloP100		-0.31
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: rs1343548; hg19: chr1-165215106;