rs2289278

Positions:

• chr5-111073450-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000379706.4(TSLP):​c.-133C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,607,470 control chromosomes in the GnomAD database, including 5,728 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 0.088 (755 hom., cov: 32)
  • Exomes 𝑓: 0.072 (4973 hom.)
• Consequence: TSLP ENST00000379706.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

Genes affected

TSLP (HGNC:30743): (thymic stromal lymphopoietin) This gene encodes a hemopoietic cytokine proposed to signal through a heterodimeric receptor complex composed of the thymic stromal lymphopoietin receptor and the IL-7R alpha chain. It mainly impacts myeloid cells and induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of CD11c(+) dendritic cells. The protein promotes T helper type 2 (TH2) cell responses that are associated with immunity in various inflammatory diseases, including asthma, allergic inflammation and chronic obstructive pulmonary disease. The protein is therefore considered a potential therapeutic target for the treatment of such diseases. In addition, the shorter (predominant) isoform is an antimicrobial protein, displaying antibacterial and antifungal activity against B. cereus, E. coli, E. faecalis, S. mitis, S. epidermidis, and C. albicans. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSLP	NM_033035.5	c.217-61C>G		intron_variant		ENST00000344895.4	NP_149024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000379706.4	c.-133C>G		5_prime_UTR_variant	1/2	1		ENSP00000427827
TSLP	ENST00000344895.4	c.217-61C>G		intron_variant		1	NM_033035.5	ENSP00000339804	P4
TSLP	ENST00000420978.6	c.217-61C>G		intron_variant		1		ENSP00000399099	A2

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13403 AN: 152124 Hom.: 754 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0771

GnomAD4 exome AF: 0.0724 AC: 105293 AN: 1455228 Hom.: 4973 Cov.: 33 AF XY: 0.0728 AC XY: 52639 AN XY: 723324

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0603

Gnomad4 OTH exome AF: 0.0787

GnomAD4 genome AF: 0.0881 AC: 13415 AN: 152242 Hom.: 755 Cov.: 32 AF XY: 0.0893 AC XY: 6645 AN XY: 74436

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0705 Hom.: 56

Bravo AF: 0.0965

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.83
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2289278; hg19: chr5-110409148;