rs2289276

Positions:

• chr5-111071809-C-T

Variant summary

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

The NM_033035.5(TSLP):​c.-82C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,520,870 control chromosomes in the GnomAD database, including 70,795 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 0.28 (6236 hom., cov: 33)
  • Exomes 𝑓: 0.30 (64559 hom.)
• Consequence: TSLP NM_033035.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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]

TSLP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSLP	NM_033035.5	c.-82C>T		5_prime_UTR_variant	1/4	ENST00000344895.4	NP_149024.1
TSLP	XM_047417846.1	c.4+63C>T		intron_variant			XP_047273802.1
TSLP	XM_047417847.1	c.-128-116C>T		intron_variant			XP_047273803.1
TSLP	NR_045089.2	n.1457-116C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.-82C>T		5_prime_UTR_variant	1/4	1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000420978.6	c.35-116C>T		intron_variant		1		ENSP00000399099.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41914 AN: 152080 Hom.: 6230 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.303 AC: 414714 AN: 1368672 Hom.: 64559 Cov.: 23 AF XY: 0.306 AC XY: 207261 AN XY: 676560

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.275 AC: 41930 AN: 152198 Hom.: 6236 Cov.: 33 AF XY: 0.283 AC XY: 21045 AN XY: 74412

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.297

Alfa AF: 0.297 Hom.: 9225

Bravo AF: 0.267

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.6
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2289276; hg19: chr5-110407507; COSMIC: COSV61291363; COSMIC: COSV61291363;