chr16-1229574-G-A

Variant names:

• chr16-1229574-G-A
• rs745594960
• NM_024164.6:c.225C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024164.6(TPSB2):​c.225C>T​(p.Cys75Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,407,030 control chromosomes in the GnomAD database, including 1 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: not found (cov: 20)
  • Exomes 𝑓: 0.0000050 (1 hom.)
• Consequence: TPSB2 NM_024164.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.54 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSB2	NM_024164.6	c.225C>T	p.Cys75Cys	synonymous_variant	Exon 3 of 6	ENST00000606293.5	NP_077078.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSB2	ENST00000606293.5	c.225C>T	p.Cys75Cys	synonymous_variant	Exon 3 of 6	1	NM_024164.6	ENSP00000482743.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.0000106 AC: 2 AN: 188832 AF XY: 0.0000195

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000166

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000498 AC: 7 AN: 1407030 Hom.: 1 Cov.: 41 AF XY: 0.00000287 AC XY: 2 AN XY: 696904

African (AFR) AF: 0.00 AC: 0 AN: 30010

American (AMR) AF: 0.00 AC: 0 AN: 35784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22820

East Asian (EAS) AF: 0.00 AC: 0 AN: 37374

South Asian (SAS) AF: 0.00 AC: 0 AN: 75740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4446

European-Non Finnish (NFE) AF: 0.00000458 AC: 5 AN: 1092742

Other (OTH) AF: 0.0000345 AC: 2 AN: 57926

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs745594960; hg19: chr16-1279575;