Variant rs55827759 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000460.4(THPO):c.229-14_229-13insTTCC variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,613,588 control chromosomes in the GnomAD database, including 1,094 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 113 hom., cov: 32)

Exomes 𝑓: 0.034 ( 981 hom. )

Consequence

THPO
NM_000460.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.89

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 -16 ACMG points.

BP6

Variant 3-184373595-T-TGGAA is Benign according to our data. Variant chr3-184373595-T-TGGAA is described in ClinVar as [Likely_benign]. Clinvar id is 256212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0351 (5341/152076) while in subpopulation AFR AF= 0.0438 (1816/41476). AF 95% confidence interval is 0.0421. There are 113 homozygotes in gnomad4. There are 2590 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 113 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THPO	NM_000460.4 linkuse as main transcript	c.229-14_229-13insTTCC		splice_polypyrimidine_tract_variant, 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.229-14_229-13insTTCC		splice_polypyrimidine_tract_variant, intron_variant			NM_000460.4	ENSP00000494504	P2	P40225-1

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5327

AN:

151958

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0300

AC:

7520

AN:

250498

Hom.:

134

AF XY:

0.0302

AC XY:

4096

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.0446

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0244

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0367

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0344

AC:

50227

AN:

1461512

Hom.:

981

Cov.:

AF XY:

0.0342

AC XY:

24851

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0500

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0242

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0366

Gnomad4 OTH exome

AF:

0.0353

GnomAD4 genome

AF:

0.0351

AC:

5341

AN:

152076

Hom.:

113

Cov.:

AF XY:

0.0348

AC XY:

2590

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0438

Gnomad4 AMR

AF:

0.0275

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0366

Hom.:

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Thrombocythemia 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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