1-165206137-G-C

Variant names:

• chr1-165206137-G-C
• rs4656435
• NM_177398.4:c.818-103C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177398.4(LMX1A):​c.818-103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• 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-AS2 (HGNC:40343): (LMX1A antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.818-103C>G		intron_variant	Intron 7 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.818-103C>G		intron_variant	Intron 7 of 8		NP_001167540.1
LMX1A	XM_011509538.4	c.578-103C>G		intron_variant	Intron 5 of 6		XP_011507840.1
LMX1A-AS2	XR_922234.2	n.366+367G>C		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.818-103C>G		intron_variant	Intron 7 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.818-103C>G		intron_variant	Intron 6 of 7	1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.452-103C>G		intron_variant	Intron 5 of 6	1
LMX1A	ENST00000294816.6	c.818-103C>G		intron_variant	Intron 7 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 951060 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 476730

African (AFR) AF: 0.00 AC: 0 AN: 20868

American (AMR) AF: 0.00 AC: 0 AN: 22626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16604

East Asian (EAS) AF: 0.00 AC: 0 AN: 33348

South Asian (SAS) AF: 0.00 AC: 0 AN: 54866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 710050

Other (OTH) AF: 0.00 AC: 0 AN: 41808

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		1.9

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: rs4656435; hg19: chr1-165175374;