chr1-165204312-G-A

Position:

• chr1-165204312-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177398.4(LMX1A):​c.989-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,032 control chromosomes in the GnomAD database, including 19,099 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 0.48 (19099 hom., cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.989-272C>T		intron_variant		ENST00000342310.7	NP_796372.1
LMX1A-AS2	XR_922234.2	n.101+165G>A		intron_variant, non_coding_transcript_variant
LMX1A	NM_001174069.2	c.989-272C>T		intron_variant			NP_001167540.1
LMX1A	XM_011509538.4	c.749-272C>T		intron_variant			XP_011507840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.989-272C>T		intron_variant		2	NM_177398.4	ENSP00000340226	P1
LMX1A	ENST00000367893.4	c.989-272C>T		intron_variant		1		ENSP00000356868	P1
LMX1A	ENST00000489443.2	n.623-272C>T		intron_variant, non_coding_transcript_variant		1
LMX1A	ENST00000294816.6	c.989-272C>T		intron_variant		2		ENSP00000294816	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72408 AN: 151912 Hom.: 19095 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.476 AC: 72424 AN: 152032 Hom.: 19099 Cov.: 32 AF XY: 0.473 AC XY: 35129 AN XY: 74326

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.488

Alfa AF: 0.569 Hom.: 23985

Bravo AF: 0.455

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs4657411; hg19: chr1-165173549;