Genetic Variant TPSB2:n.*111-3T>C (chr16-1227472-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000611196.4(TPSB2):n.*111-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,870 control chromosomes in the GnomAD database, including 47,186 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 0.78 ( 47186 hom., cov: 35)

Exomes 𝑓: 0.79 ( 520 hom. )

Failed GnomAD Quality Control

Consequence

TPSB2
ENST00000611196.4 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

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:

LOC124903621 (HGNC:):

LOC124903621 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903621	XM_047434997.1 link	c.*232A>G		downstream_gene_variant			XP_047290953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSB2	ENST00000611196.4 link	n.*111-3T>C		splice_region_variant, intron_variant	Intron 7 of 7	1		ENSP00000484461.1		A0A087X1U0

Frequencies

GnomAD3 genomes

AF:

0.783

AC:

118753

AN:

151750

Hom.:

47120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.812

Gnomad EAS

AF:

0.974

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.704

Gnomad OTH

AF:

0.790

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.786

AC:

1304

AN:

1658

Hom.:

520

Cov.:

AF XY:

0.767

AC XY:

704

AN XY:

918

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.803

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.850

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.742

AC:

196

AN:

264

European-Finnish (FIN)

AF:

0.864

AC:

114

AN:

132

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.786

AC:

835

AN:

1062

Other (OTH)

AF:

0.676

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.783

AC:

118880

AN:

151870

Hom.:

47186

Cov.:

AF XY:

0.786

AC XY:

58385

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.887

AC:

36763

AN:

41464

American (AMR)

AF:

0.797

AC:

12175

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.812

AC:

2820

AN:

3472

East Asian (EAS)

AF:

0.975

AC:

5058

AN:

5190

South Asian (SAS)

AF:

0.688

AC:

3285

AN:

4772

European-Finnish (FIN)

AF:

0.800

AC:

8467

AN:

10586

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.704

AC:

47709

AN:

67804

Other (OTH)

AF:

0.792

AC:

1670

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

1339

2678

4017

5356

6695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.753

Hom.:

9439

Bravo

AF:

0.790

Asia WGS

AF:

0.834

AC:

2901

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.1

(source)

DANN

Benign

0.51

PhyloP100

-0.12

Splicing

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.

16-1227472-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over