rs1395548

Variant names:

• chr1-165344190-A-C
• rs1395548
• NM_177398.4:c.263+8886T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-165344190-A-C
• chr1-165344190-A-G
• chr1-165344190-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.263+8886T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,154 control chromosomes in the GnomAD database, including 24,526 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 0.55 (24526 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 8 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 7

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	NM_177398.4	MANE Select	c.263+8886T>G		intron	N/A	NP_796372.1
	LMX1A	NM_001174069.2		c.263+8886T>G		intron	N/A	NP_001167540.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	ENST00000342310.7	TSL:2 MANE Select	c.263+8886T>G		intron	N/A	ENSP00000340226.3
	LMX1A	ENST00000367893.4	TSL:1	c.263+8886T>G		intron	N/A	ENSP00000356868.4
	LMX1A	ENST00000294816.6	TSL:2	c.263+8886T>G		intron	N/A	ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84334 AN: 152036 Hom.: 24531 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.554 AC: 84352 AN: 152154 Hom.: 24526 Cov.: 32 AF XY: 0.559 AC XY: 41595 AN XY: 74388

African (AFR) AF: 0.371 AC: 15422 AN: 41516

American (AMR) AF: 0.604 AC: 9237 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4020 AN: 5154

South Asian (SAS) AF: 0.559 AC: 2700 AN: 4828

European-Finnish (FIN) AF: 0.663 AC: 7029 AN: 10602

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41768 AN: 67984

Other (OTH) AF: 0.564 AC: 1192 AN: 2114

Alfa AF: 0.593 Hom.: 85485

Bravo AF: 0.544

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.72
PhyloP100		0.22
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: rs1395548; hg19: chr1-165313427;