rs3804618

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

thrombocythemia 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
congenital amegakaryocytic thrombocytopenia
Inheritance: SD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
thrombocytopenia 9
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
familial thrombocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary isolated aplastic anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary thrombocytosis with transverse limb defect
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital amegakaryocytic thrombocytopenia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

THPO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THPO	NM_000460.4	MANE Select	c.*482A>T	3_prime_UTR	Exon 6 of 6	NP_000451.1	P40225-1
THPO	NM_001290003.1		c.*482A>T	3_prime_UTR	Exon 7 of 7	NP_001276932.1	A0A3B3ITS0
THPO	NM_001289998.1		c.*482A>T	3_prime_UTR	Exon 7 of 7	NP_001276927.1	P40225-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THPO	ENST00000647395.1	MANE Select	c.*482A>T	3_prime_UTR	Exon 6 of 6	ENSP00000494504.1	P40225-1
THPO	ENST00000649095.1		c.*482A>T	3_prime_UTR	Exon 7 of 7	ENSP00000497904.1	A0A3B3ITS0
THPO	ENST00000876541.1		c.*482A>T	3_prime_UTR	Exon 6 of 6	ENSP00000546600.1

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

African (AFR)

AF:

0.0632

AC:

AN:

570

American (AMR)

AF:

0.0277

AC:

AN:

3100

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

AN:

334

East Asian (EAS)

AF:

0.0819

AC:

136

AN:

1660

South Asian (SAS)

AF:

0.0362

AC:

AN:

2184

European-Finnish (FIN)

AF:

0.0367

AC:

AN:

762

Middle Eastern (MID)

AF:

0.0333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0526

AC:

453

AN:

8606

Other (OTH)

AF:

0.0487

AC:

AN:

616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0630

AC:

9589

AN:

152324

Hom.:

315

Cov.:

AF XY:

0.0605

AC XY:

4510

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0801

AC:

3328

AN:

41558

American (AMR)

AF:

0.0343

AC:

525

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0544

AC:

189

AN:

3472

East Asian (EAS)

AF:

0.109

AC:

568

AN:

5192

South Asian (SAS)

AF:

0.0513

AC:

248

AN:

4832

European-Finnish (FIN)

AF:

0.0386

AC:

410

AN:

10620

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0609

AC:

4144

AN:

68024

Other (OTH)

AF:

0.0629

AC:

133

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

465

930

1395

1860

2325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0256

Hom.:

Bravo

AF:

0.0641

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Thrombocythemia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.8

(source)

DANN

Benign

0.68

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over