Variant 3-184375739-C-T 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.142-138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 1,480,742 control chromosomes in the GnomAD database, including 6,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 783 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6172 hom. )

Consequence

THPO
NM_000460.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-184375739-C-T is Benign according to our data. Variant chr3-184375739-C-T is described in ClinVar as [Benign]. Clinvar id is 1265627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THPO	NM_000460.4 linkuse as main transcript	c.142-138G>A		intron_variant		ENST00000647395.1	NP_000451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THPO	ENST00000647395.1 linkuse as main transcript	c.142-138G>A		intron_variant			NM_000460.4	ENSP00000494504	P2	P40225-1

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15215

AN:

152014

Hom.:

782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0749

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0730

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0882

Gnomad OTH

AF:

0.0958

GnomAD4 exome

AF:

0.0926

AC:

123030

AN:

1328610

Hom.:

6172

Cov.:

AF XY:

0.0915

AC XY:

61057

AN XY:

666964

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0690

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.0711

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0892

Gnomad4 OTH exome

AF:

0.0860

GnomAD4 genome

AF:

0.100

AC:

15229

AN:

152132

Hom.:

783

Cov.:

AF XY:

0.101

AC XY:

7508

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0749

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.0730

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.0882

Gnomad4 OTH

AF:

0.0938

Alfa

AF:

0.0909

Hom.:

696

Bravo

AF:

0.103

Asia WGS

AF:

0.0990

AC:

346

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.76

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