3-184378790-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000691896.2(ENSG00000289500):​n.559A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 984,546 control chromosomes in the GnomAD database, including 122,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 18937 hom., cov: 32)
Exomes 𝑓: 0.50 ( 103495 hom. )

Consequence


ENST00000691896.2 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.37
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THPONM_001289998.1 linkuse as main transcriptc.-448-413T>C intron_variant
THPONM_001290003.1 linkuse as main transcriptc.-28-413T>C intron_variant
THPONM_001290022.1 linkuse as main transcriptc.-448-413T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ENST00000691896.2 linkuse as main transcriptn.559A>G non_coding_transcript_exon_variant 1/1
THPOENST00000645603.2 linkuse as main transcriptc.-28-413T>C intron_variant A2
THPOENST00000649095.1 linkuse as main transcriptc.-28-413T>C intron_variant A2

Frequencies

GnomAD3 genomes
AF:
0.494
AC:
75118
AN:
151918
Hom.:
18916
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.517
Gnomad AMI
AF:
0.451
Gnomad AMR
AF:
0.597
Gnomad ASJ
AF:
0.565
Gnomad EAS
AF:
0.372
Gnomad SAS
AF:
0.453
Gnomad FIN
AF:
0.347
Gnomad MID
AF:
0.585
Gnomad NFE
AF:
0.488
Gnomad OTH
AF:
0.541
GnomAD4 exome
AF:
0.497
AC:
414169
AN:
832510
Hom.:
103495
Cov.:
29
AF XY:
0.497
AC XY:
190935
AN XY:
384464
show subpopulations
Gnomad4 AFR exome
AF:
0.526
Gnomad4 AMR exome
AF:
0.635
Gnomad4 ASJ exome
AF:
0.551
Gnomad4 EAS exome
AF:
0.373
Gnomad4 SAS exome
AF:
0.460
Gnomad4 FIN exome
AF:
0.359
Gnomad4 NFE exome
AF:
0.497
Gnomad4 OTH exome
AF:
0.511
GnomAD4 genome
AF:
0.495
AC:
75188
AN:
152036
Hom.:
18937
Cov.:
32
AF XY:
0.489
AC XY:
36330
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.517
Gnomad4 AMR
AF:
0.596
Gnomad4 ASJ
AF:
0.565
Gnomad4 EAS
AF:
0.372
Gnomad4 SAS
AF:
0.455
Gnomad4 FIN
AF:
0.347
Gnomad4 NFE
AF:
0.488
Gnomad4 OTH
AF:
0.540
Alfa
AF:
0.501
Hom.:
25960
Bravo
AF:
0.515
Asia WGS
AF:
0.453
AC:
1579
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.16
DANN
Benign
0.38

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.

Other links and lift over

dbSNP: rs885838; hg19: chr3-184096578; API