chr1-165210852-T-A

Position:

• chr1-165210852-T-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.670-76A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,018,780 control chromosomes in the GnomAD database, including 279,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46753 hom., cov: 32)
  • Exomes 𝑓: 0.72 (232898 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.922

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-165210852-T-A is Benign according to our data. Variant chr1-165210852-T-A is described in ClinVar as [Benign]. Clinvar id is 1225418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.670-76A>T		intron_variant		ENST00000342310.7	NP_796372.1
LMX1A-AS2	XR_922234.2	n.789T>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.670-76A>T		intron_variant		2	NM_177398.4	ENSP00000340226	P1
LMX1A-AS2	ENST00000457106.1	n.226T>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117336 AN: 152020 Hom.: 46708 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 0.724 AC: 627878 AN: 866642 Hom.: 232898 Cov.: 11 AF XY: 0.721 AC XY: 320556 AN XY: 444598

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.763

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome AF: 0.772 AC: 117431 AN: 152138 Hom.: 46753 Cov.: 32 AF XY: 0.761 AC XY: 56607 AN XY: 74356

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.763

Alfa AF: 0.730 Hom.: 20034

Bravo AF: 0.772

Asia WGS AF: 0.510 AC: 1773 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	-0.91
CADD	Benign	0.13
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1532815; hg19: chr1-165180089; COSMIC: COSV54216452;