rs16841013

Positions:

• chr1-165205722-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177398.4(LMX1A):​c.988+142G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 706,182 control chromosomes in the GnomAD database, including 25,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4390 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21356 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.370

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-165205722-C-T is Benign according to our data. Variant chr1-165205722-C-T is described in ClinVar as [Benign]. Clinvar id is 1236257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.988+142G>A		intron_variant		ENST00000342310.7	NP_796372.1
LMX1A-AS2	XR_922234.2	n.318C>T		non_coding_transcript_exon_variant	2/6
LMX1A	NM_001174069.2	c.988+142G>A		intron_variant			NP_001167540.1
LMX1A	XM_011509538.4	c.748+142G>A		intron_variant			XP_011507840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.988+142G>A		intron_variant		2	NM_177398.4	ENSP00000340226	P1
LMX1A	ENST00000367893.4	c.988+142G>A		intron_variant		1		ENSP00000356868	P1
LMX1A	ENST00000489443.2	n.622+142G>A		intron_variant, non_coding_transcript_variant		1
LMX1A	ENST00000294816.6	c.988+142G>A		intron_variant		2		ENSP00000294816	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32004 AN: 151996 Hom.: 4386 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.262 AC: 145398 AN: 554068 Hom.: 21356 AF XY: 0.266 AC XY: 77688 AN XY: 292012

Gnomad4 AFR exome AF: 0.0584

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.210 AC: 32019 AN: 152114 Hom.: 4390 Cov.: 32 AF XY: 0.220 AC XY: 16373 AN XY: 74346

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.218

Alfa AF: 0.234 Hom.: 4271

Bravo AF: 0.208

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.78

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: rs16841013; hg19: chr1-165174959;