16-1227472-A-G

Position:

• chr16-1227472-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611196.4(TPSB2):​c.*111-3T>C variant causes a splice region, splice polypyrimidine tract, intron, NMD transcript 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, splice_polypyrimidine_tract, intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPSB2	ENST00000611196.4	c.*111-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118753 AN: 151750 Hom.: 47120 Cov.: 35

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.: 0 AF XY: 0.767 AC XY: 704 AN XY: 918

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.803

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.864

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.783 AC: 118880 AN: 151870 Hom.: 47186 Cov.: 35 AF XY: 0.786 AC XY: 58385 AN XY: 74248

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.792

Alfa AF: 0.679 Hom.: 3178

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
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2745145; hg19: chr16-1277472;