chr1-165340949-C-G

Variant names:

• chr1-165340949-C-G
• rs6702087
• NM_177398.4:c.263+12127G>C

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+12127G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,150 control chromosomes in the GnomAD database, including 61,191 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 0.90 (61191 hom., cov: 30)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.263+12127G>C		intron_variant	Intron 3 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.263+12127G>C		intron_variant	Intron 3 of 8		NP_001167540.1
LMX1A	XM_011509540.3	c.263+12127G>C		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+12127G>C		intron_variant	Intron 3 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.263+12127G>C		intron_variant	Intron 2 of 7	1		ENSP00000356868.4
LMX1A	ENST00000294816.6	c.263+12127G>C		intron_variant	Intron 3 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136076 AN: 152032 Hom.: 61146 Cov.: 30

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.895 AC: 136179 AN: 152150 Hom.: 61191 Cov.: 30 AF XY: 0.892 AC XY: 66375 AN XY: 74390

African (AFR) AF: 0.816 AC: 33836 AN: 41470

American (AMR) AF: 0.904 AC: 13817 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3212 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4893 AN: 5176

South Asian (SAS) AF: 0.850 AC: 4090 AN: 4810

European-Finnish (FIN) AF: 0.916 AC: 9709 AN: 10600

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63638 AN: 68024

Other (OTH) AF: 0.891 AC: 1879 AN: 2108

Alfa AF: 0.901 Hom.: 2978

Bravo AF: 0.890

Asia WGS AF: 0.873 AC: 3037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.48
PhyloP100		0.21
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: rs6702087; hg19: chr1-165310186;