rs2289278

Variant names:

• chr5-111073450-C-G
• rs2289278
• ENST00000379706.4:c.-133C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TSLP	NM_033035.5	c.217-61C>G		intron_variant	Intron 2 of 3	ENST00000344895.4	NP_149024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000379706.4	c.-133C>G		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000427827.1
TSLP	ENST00000344895.4	c.217-61C>G		intron_variant	Intron 2 of 3	1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000420978.6	c.217-61C>G		intron_variant	Intron 3 of 4	1		ENSP00000399099.2

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

African (AFR) AF: 0.117 AC: 3893 AN: 33196

American (AMR) AF: 0.197 AC: 8648 AN: 43956

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 1152 AN: 25698

East Asian (EAS) AF: 0.199 AC: 7907 AN: 39636

South Asian (SAS) AF: 0.117 AC: 9952 AN: 85172

European-Finnish (FIN) AF: 0.0351 AC: 1865 AN: 53158

Middle Eastern (MID) AF: 0.0484 AC: 277 AN: 5722

European-Non Finnish (NFE) AF: 0.0603 AC: 66869 AN: 1108608

Other (OTH) AF: 0.0787 AC: 4730 AN: 60082

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

African (AFR) AF: 0.114 AC: 4732 AN: 41544

American (AMR) AF: 0.137 AC: 2094 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5162

South Asian (SAS) AF: 0.137 AC: 658 AN: 4820

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4016 AN: 68028

Other (OTH) AF: 0.0782 AC: 165 AN: 2110

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
PhyloP100		-1.8
PromoterAI		0.088	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289278; hg19: chr5-110409148;