Variant 1-165207933-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0160

Variant links:

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 links:

LMX1A-AS2 (HGNC:40343): (LMX1A antisense RNA 2)

LMX1A-AS2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
LMX1A	NM_177398.4 linkuse as main transcript	c.817+130A>G		intron_variant		ENST00000342310.7	NP_796372.1	Q8TE12-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LMX1A	ENST00000342310.7 linkuse as main transcript	c.817+130A>G	intron_variant	2	NM_177398.4	ENSP00000340226.3	Q8TE12-1
LMX1A	ENST00000367893.4 linkuse as main transcript	c.817+130A>G	intron_variant	1		ENSP00000356868.4	Q8TE12-1
LMX1A	ENST00000489443.2 linkuse as main transcript	n.318+130A>G	intron_variant	1
LMX1A	ENST00000294816.6 linkuse as main transcript	c.817+130A>G	intron_variant	2		ENSP00000294816.2	Q8TE12-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32634

AN:

152002

Hom.:

4409

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.210

AC XY:

15606

AN XY:

74370

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over