1-165206137-G-A

Position:

• chr1-165206137-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177398.4(LMX1A):​c.818-103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,100,484 control chromosomes in the GnomAD database, including 216,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25688 hom., cov: 32)
  • Exomes 𝑓: 0.63 (191159 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.87

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-165206137-G-A is Benign according to our data. Variant chr1-165206137-G-A is described in ClinVar as [Benign]. Clinvar id is 1294822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.818-103C>T		intron_variant		ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.818-103C>T		intron_variant			NP_001167540.1
LMX1A	XM_011509538.4	c.578-103C>T		intron_variant			XP_011507840.1
LMX1A-AS2	XR_922234.2	n.366+367G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.818-103C>T		intron_variant		2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.818-103C>T		intron_variant		1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.452-103C>T		intron_variant		1
LMX1A	ENST00000294816.6	c.818-103C>T		intron_variant		2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86939 AN: 151914 Hom.: 25672 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.628 AC: 595454 AN: 948452 Hom.: 191159 AF XY: 0.624 AC XY: 296662 AN XY: 475456

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.668

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.572 AC: 86997 AN: 152032 Hom.: 25688 Cov.: 32 AF XY: 0.566 AC XY: 42039 AN XY: 74320

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.587

Alfa AF: 0.629 Hom.: 16327

Bravo AF: 0.557

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.68

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: rs4656435; hg19: chr1-165175374;