rs11809911

Variant names:

• chr1-165319120-T-C
• rs11809911
• NM_177398.4:c.263+33956A>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.263+33956A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,714 control chromosomes in the GnomAD database, including 23,496 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 (23496 hom., cov: 30)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• 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 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.263+33956A>G		intron_variant	Intron 3 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.263+33956A>G		intron_variant	Intron 3 of 8		NP_001167540.1
LMX1A	XM_011509540.3	c.263+33956A>G		intron_variant	Intron 3 of 7		XP_011507842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.263+33956A>G		intron_variant	Intron 3 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.263+33956A>G		intron_variant	Intron 2 of 7	1		ENSP00000356868.4
LMX1A	ENST00000294816.6	c.263+33956A>G		intron_variant	Intron 3 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83656 AN: 151594 Hom.: 23467 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.552 AC: 83735 AN: 151714 Hom.: 23496 Cov.: 30 AF XY: 0.546 AC XY: 40483 AN XY: 74108

African (AFR) AF: 0.554 AC: 22914 AN: 41334

American (AMR) AF: 0.521 AC: 7943 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1853 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5162

South Asian (SAS) AF: 0.465 AC: 2235 AN: 4806

European-Finnish (FIN) AF: 0.576 AC: 6047 AN: 10494

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.582 AC: 39507 AN: 67906

Other (OTH) AF: 0.531 AC: 1119 AN: 2108

Alfa AF: 0.570 Hom.: 100747

Bravo AF: 0.549

Asia WGS AF: 0.399 AC: 1386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.77
PhyloP100		-0.24
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: rs11809911; hg19: chr1-165288357;