chr1-165210637-C-A

Position:

• chr1-165210637-C-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.747+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,265,156 control chromosomes in the GnomAD database, including 3,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (1678 hom., cov: 33)
  • Exomes 𝑓: 0.023 (1358 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0600

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=-0.8).
• BP6: Variant 1-165210637-C-A is Benign according to our data. Variant chr1-165210637-C-A is described in ClinVar as [Benign]. Clinvar id is 1244331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMX1A	NM_177398.4	c.747+62G>T		intron_variant		ENST00000342310.7
LMX1A-AS2	XR_922234.2	n.574C>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMX1A	ENST00000342310.7	c.747+62G>T		intron_variant		2	NM_177398.4	P1
LMX1A-AS2	ENST00000457106.1	n.11C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13762 AN: 152034 Hom.: 1674 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0819

GnomAD4 exome AF: 0.0228 AC: 25404 AN: 1113004 Hom.: 1358 Cov.: 14 AF XY: 0.0215 AC XY: 12208 AN XY: 567988

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.0367

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00587

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.0145

Gnomad4 OTH exome AF: 0.0395

GnomAD4 genome AF: 0.0906 AC: 13780 AN: 152152 Hom.: 1678 Cov.: 33 AF XY: 0.0877 AC XY: 6521 AN XY: 74378

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.0539

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0322 Hom.: 395

Bravo AF: 0.104

Asia WGS AF: 0.0220 AC: 77 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 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.47

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: rs6703000; hg19: chr1-165179874;