rs199887053
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_024164.6(TPSB2):c.226G>C(p.Val76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,320,564 control chromosomes in the GnomAD database, including 93,140 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.46 ( 14869 hom., cov: 18)
Exomes 𝑓: 0.40 ( 78271 hom. )
Consequence
TPSB2
NM_024164.6 missense
NM_024164.6 missense
Scores
12
Clinical Significance
Conservation
PhyloP100: -4.62
Genes affected
TPSB2 (HGNC:14120): (tryptase beta 2) Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. These genes are characterized by several distinct features. They have a highly conserved 3' UTR and contain tandem repeat sequences at the 5' flank and 3' UTR which are thought to play a role in regulation of the mRNA stability. These genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. The alleles of this gene exhibit an unusual amount of sequence variation, such that the alleles were once thought to represent two separate genes, beta II and beta III. Beta tryptases appear to be the main isoenzymes expressed in mast cells, whereas in basophils, alpha-tryptases predominate. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=5.68062E-6).
BP6
?
Variant 16-1229573-C-G is Benign according to our data. Variant chr16-1229573-C-G is described in ClinVar as [Benign]. Clinvar id is 403561.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPSB2 | NM_024164.6 | c.226G>C | p.Val76Leu | missense_variant | 3/6 | ENST00000606293.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPSB2 | ENST00000606293.5 | c.226G>C | p.Val76Leu | missense_variant | 3/6 | 1 | NM_024164.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.464 AC: 55704AN: 120138Hom.: 14862 Cov.: 18
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GnomAD3 exomes AF: 0.347 AC: 46625AN: 134232Hom.: 9178 AF XY: 0.346 AC XY: 25035AN XY: 72358
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GnomAD4 exome AF: 0.401 AC: 481570AN: 1200344Hom.: 78271 Cov.: 36 AF XY: 0.404 AC XY: 240155AN XY: 595172
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GnomAD4 genome ? AF: 0.464 AC: 55740AN: 120220Hom.: 14869 Cov.: 18 AF XY: 0.465 AC XY: 26867AN XY: 57792
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P
PrimateAI
Benign
T
Sift4G
Benign
T;T
Vest4
MutPred
Gain of catalytic residue at V76 (P = 0.0731);.;
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at