chr16-1229573-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 11/14 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.62

Publications

11 publications found

Variant links:

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]

TPSB2 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 (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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TPSB2	NM_024164.6 link	c.226G>C	p.Val76Leu	missense_variant	Exon 3 of 6	ENST00000606293.5	NP_077078.5	P20231A0A140VJT7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSB2	ENST00000606293.5 link	c.226G>C	p.Val76Leu	missense_variant	Exon 3 of 6	1	NM_024164.6	ENSP00000482743.1		P20231

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

55704

AN:

120138

Hom.:

14862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.371

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.445

GnomAD2 exomes

AF:

0.347

AC:

46625

AN:

134232

AF XY:

0.346

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.401

AC:

481570

AN:

1200344

Hom.:

78271

Cov.:

AF XY:

0.404

AC XY:

240155

AN XY:

595172

show subpopulations

African (AFR)

AF:

0.345

AC:

9712

AN:

28128

American (AMR)

AF:

0.332

AC:

10506

AN:

31608

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

8238

AN:

20594

East Asian (EAS)

AF:

0.775

AC:

27833

AN:

35926

South Asian (SAS)

AF:

0.417

AC:

28547

AN:

68462

European-Finnish (FIN)

AF:

0.608

AC:

28198

AN:

46342

Middle Eastern (MID)

AF:

0.376

AC:

1506

AN:

4004

European-Non Finnish (NFE)

AF:

0.378

AC:

345592

AN:

914174

Other (OTH)

AF:

0.419

AC:

21438

AN:

51106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

9371

18742

28112

37483

46854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.464

AC:

55740

AN:

120220

Hom.:

14869

Cov.:

AF XY:

0.465

AC XY:

26867

AN XY:

57792

show subpopulations

African (AFR)

AF:

0.384

AC:

11080

AN:

28890

American (AMR)

AF:

0.414

AC:

5073

AN:

12240

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1349

AN:

3108

East Asian (EAS)

AF:

0.789

AC:

2313

AN:

2930

South Asian (SAS)

AF:

0.450

AC:

1502

AN:

3336

European-Finnish (FIN)

AF:

0.631

AC:

5059

AN:

8012

Middle Eastern (MID)

AF:

0.360

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.478

AC:

28216

AN:

59058

Other (OTH)

AF:

0.443

AC:

720

AN:

1626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

899

1798

2696

3595

4494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.350

AC:

40134

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Benign

1.7

(source)

DANN

Benign

0.70

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.0000057

T;T

MetaSVM

Benign

-0.91

PhyloP100

-4.6

PrimateAI

Benign

0.46

Sift4G

Benign

0.39

T;T

Vest4

0.046

MutPred

0.66

Gain of catalytic residue at V76 (P = 0.0731);.;

ClinPred

0.0053

GERP RS

-4.6

gMVP

0.27

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr16-1229573-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over