rs201836020

chr16-1229731-C-Achr16-1229731-C-Gchr16-1229731-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024164.6(TPSB2):c.68G>T(p.Gly23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (57 hom., cov: 25)
  • Exomes 𝑓: 0.22 (609 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPSB2 NM_024164.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002231419).
• BP6: Variant 16-1229731-C-A is Benign according to our data. Variant chr16-1229731-C-A is described in ClinVar as [Benign]. Clinvar id is 403562.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPSB2	NM_024164.6	c.68G>T	p.Gly23Val	missense_variant	3/6	ENST00000606293.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPSB2	ENST00000606293.5	c.68G>T	p.Gly23Val	missense_variant	3/6	1	NM_024164.6	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 42146 AN: 128340 Hom.: 57 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.286

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.326

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.225 AC: 234565 AN: 1043948 Hom.: 609 Cov.: 71 AF XY: 0.235 AC XY: 123824 AN XY: 527044

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.328 AC: 42166 AN: 128432 Hom.: 57 Cov.: 25 AF XY: 0.330 AC XY: 20686 AN XY: 62726

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.323

Alfa AF: 0.228 Hom.: 40

ExAC AF: 0.243 AC: 29238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 (fails quality filter) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	11
Dann	Benign	0.96
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.50	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.64	T
Sift4G	Benign	0.33	T;T
Vest4		0.10
ClinPred		0.019	T
GERP RS		0.77
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201836020; hg19: chr16-1279732; COSMIC: COSV52352433; COSMIC: COSV52352433;