Variant 3-184372031-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000460.4(THPO):c.*482A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 170,186 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 315 hom., cov: 33)

Exomes 𝑓: 0.048 ( 34 hom. )

Consequence

THPO
NM_000460.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.172

Variant links:

Genes affected

THPO (HGNC:11795): (thrombopoietin) Megakaryocytopoiesis is the cellular development process that leads to platelet production. The main functional protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene. Mutations in this gene are the cause of thrombocythemia 1. Alternative promoter usage and differential splicing result in multiple transcript variants differing in the 5' UTR and/or coding region. Multiple AUG codons upstream of the main open reading frame (ORF) have been identified, and these upstream AUGs inhibit translation of the main ORF at different extent. [provided by RefSeq, Feb 2014]

THPO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-184372031-T-A is Benign according to our data. Variant chr3-184372031-T-A is described in ClinVar as [Benign]. Clinvar id is 344366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THPO	NM_000460.4 linkuse as main transcript	c.*482A>T		3_prime_UTR_variant	6/6	ENST00000647395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THPO	ENST00000647395.1 linkuse as main transcript	c.*482A>T		3_prime_UTR_variant	6/6		NM_000460.4	P2	P40225-1
THPO	ENST00000649095.1 linkuse as main transcript	c.*482A>T		3_prime_UTR_variant	7/7			A2

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9568

AN:

152206

Hom.:

313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0544

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0609

Gnomad OTH

AF:

0.0635

GnomAD4 exome

AF:

0.0481

AC:

860

AN:

17862

Hom.:

Cov.:

AF XY:

0.0464

AC XY:

439

AN XY:

9456

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.0277

Gnomad4 ASJ exome

AF:

0.0329

Gnomad4 EAS exome

AF:

0.0819

Gnomad4 SAS exome

AF:

0.0362

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.0487

GnomAD4 genome

AF:

0.0630

AC:

9589

AN:

152324

Hom.:

315

Cov.:

AF XY:

0.0605

AC XY:

4510

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0801

Gnomad4 AMR

AF:

0.0343

Gnomad4 ASJ

AF:

0.0544

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.0513

Gnomad4 FIN

AF:

0.0386

Gnomad4 NFE

AF:

0.0609

Gnomad4 OTH

AF:

0.0629

Alfa

AF:

0.0256

Hom.:

Bravo

AF:

0.0641

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocythemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.8

DANN

Benign

0.68

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