rs377518279

Variant names:

• chr16-1228762-G-A
• rs377518279
• NM_024164.6:c.716C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1228762-G-A
• chr16-1228762-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_024164.6(TPSB2):​c.716C>T​(p.Ala239Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,569,138 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0023 (16 hom.)
• Consequence: TPSB2 NM_024164.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0325495).
• BP6: Variant 16-1228762-G-A is Benign according to our data. Variant chr16-1228762-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSB2	NM_024164.6	c.716C>T	p.Ala239Val	missense_variant	Exon 6 of 6	ENST00000606293.5	NP_077078.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSB2	ENST00000606293.5	c.716C>T	p.Ala239Val	missense_variant	Exon 6 of 6	1	NM_024164.6	ENSP00000482743.1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 193 AN: 130472 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.000590

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00115

Gnomad ASJ AF: 0.000618

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000550

Gnomad FIN AF: 0.000434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00187 AC: 430 AN: 230022 AF XY: 0.00218

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000730

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000736

Gnomad NFE exome AF: 0.00236

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00225 AC: 3244 AN: 1438590 Hom.: 16 Cov.: 34 AF XY: 0.00233 AC XY: 1661 AN XY: 713758

African (AFR) AF: 0.000465 AC: 15 AN: 32292

American (AMR) AF: 0.000740 AC: 32 AN: 43258

Ashkenazi Jewish (ASJ) AF: 0.000236 AC: 6 AN: 25376

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38492

South Asian (SAS) AF: 0.00430 AC: 363 AN: 84410

European-Finnish (FIN) AF: 0.000823 AC: 43 AN: 52226

Middle Eastern (MID) AF: 0.000205 AC: 1 AN: 4888

European-Non Finnish (NFE) AF: 0.00244 AC: 2675 AN: 1098378

Other (OTH) AF: 0.00182 AC: 108 AN: 59270

GnomAD4 genome AF: 0.00148 AC: 193 AN: 130548 Hom.: 0 Cov.: 18 AF XY: 0.00137 AC XY: 86 AN XY: 62684

African (AFR) AF: 0.000588 AC: 19 AN: 32328

American (AMR) AF: 0.00115 AC: 15 AN: 13070

Ashkenazi Jewish (ASJ) AF: 0.000618 AC: 2 AN: 3238

East Asian (EAS) AF: 0.00 AC: 0 AN: 4252

South Asian (SAS) AF: 0.000551 AC: 2 AN: 3630

European-Finnish (FIN) AF: 0.000434 AC: 4 AN: 9206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00243 AC: 151 AN: 62046

Other (OTH) AF: 0.00 AC: 0 AN: 1684

Alfa AF: 0.00186 Hom.: 0

ESP6500AA AF: 0.000696 AC: 3

ESP6500EA AF: 0.00247 AC: 21

ExAC AF: 0.00181 AC: 218

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TPSB2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.71
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-0.63	T
PhyloP100		0.072
PrimateAI	Benign	0.41	T
Sift4G	Benign	1.0	T;T
Vest4		0.17
MVP		0.072
ClinPred		0.021	T
GERP RS		1.8
gMVP		0.27
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs377518279; hg19: chr16-1278762;