1-165207933-T-C

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.817+130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 704,076 control chromosomes in the GnomAD database, including 23,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4411 hom., cov: 32)
  • Exomes 𝑓: 0.25 (19534 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160

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=-0.84).
• BP6: Variant 1-165207933-T-C is Benign according to our data. Variant chr1-165207933-T-C is described in ClinVar as [Benign]. Clinvar id is 1294821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1A	NM_177398.4	c.817+130A>G		intron_variant		ENST00000342310.7
LMX1A-AS2	XR_922234.2	n.469+101T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1A	ENST00000342310.7	c.817+130A>G		intron_variant		2	NM_177398.4	P1
LMX1A	ENST00000367893.4	c.817+130A>G		intron_variant		1		P1
LMX1A	ENST00000489443.2	n.318+130A>G		intron_variant, non_coding_transcript_variant		1
LMX1A	ENST00000294816.6	c.817+130A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32634 AN: 152002 Hom.: 4409 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.00888

Gnomad SAS AF: 0.0803

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.247 AC: 136487 AN: 551956 Hom.: 19534 AF XY: 0.242 AC XY: 68727 AN XY: 284448

Gnomad4 AFR exome AF: 0.0866

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.00620

Gnomad4 SAS exome AF: 0.0892

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.215 AC: 32634 AN: 152120 Hom.: 4411 Cov.: 32 AF XY: 0.210 AC XY: 15606 AN XY: 74370

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.00890

Gnomad4 SAS AF: 0.0818

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.253

Alfa AF: 0.235 Hom.: 775

Bravo AF: 0.210

Asia WGS AF: 0.0640 AC: 223 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.6
Dann	Benign	0.73

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: rs17403138; hg19: chr1-165177170; COSMIC: COSV54230803; COSMIC: COSV54230803;