1-165210852-T-A

Variant names:

• chr1-165210852-T-A
• rs1532815
• NM_177398.4:c.670-76A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177398.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	NM_177398.4	MANE Select	c.670-76A>T		intron	N/A	NP_796372.1
	LMX1A	NM_001174069.2		c.670-76A>T		intron	N/A	NP_001167540.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	ENST00000342310.7	TSL:2 MANE Select	c.670-76A>T		intron	N/A	ENSP00000340226.3
	LMX1A	ENST00000367893.4	TSL:1	c.670-76A>T		intron	N/A	ENSP00000356868.4
	LMX1A	ENST00000489443.2	TSL:1	n.171-76A>T		intron	N/A

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

African (AFR) AF: 0.940 AC: 19697 AN: 20954

American (AMR) AF: 0.497 AC: 16698 AN: 33564

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 13660 AN: 19976

East Asian (EAS) AF: 0.362 AC: 12394 AN: 34244

South Asian (SAS) AF: 0.598 AC: 35587 AN: 59480

European-Finnish (FIN) AF: 0.731 AC: 35447 AN: 48492

Middle Eastern (MID) AF: 0.776 AC: 3448 AN: 4442

European-Non Finnish (NFE) AF: 0.763 AC: 461880 AN: 605638

Other (OTH) AF: 0.729 AC: 29067 AN: 39852

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

African (AFR) AF: 0.932 AC: 38723 AN: 41526

American (AMR) AF: 0.640 AC: 9780 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2308 AN: 3470

East Asian (EAS) AF: 0.355 AC: 1835 AN: 5172

South Asian (SAS) AF: 0.588 AC: 2822 AN: 4802

European-Finnish (FIN) AF: 0.718 AC: 7588 AN: 10568

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51695 AN: 67994

Other (OTH) AF: 0.763 AC: 1612 AN: 2112

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.51
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1532815; hg19: chr1-165180089; COSMIC: COSV54216452;