5-111071044-C-T

Variant summary

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

The ENST00000420978.6(TSLP):c.-440C>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 0.405 in 160,814 control chromosomes in the GnomAD database, including 14,022 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 0.40 (13188 hom., cov: 32)
  • Exomes 𝑓: 0.42 (834 hom.)
• Consequence: TSLP ENST00000420978.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSLP	XM_047417847.1	c.-129+624C>T		intron_variant
TSLP	NR_045089.2	n.983C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSLP	ENST00000420978.6	c.-440C>T		5_prime_UTR_variant	1/5	1		A2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61459 AN: 151920 Hom.: 13187 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.424 AC: 3720 AN: 8776 Hom.: 834 Cov.: 0 AF XY: 0.423 AC XY: 1931 AN XY: 4560

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.404 AC: 61477 AN: 152038 Hom.: 13188 Cov.: 32 AF XY: 0.412 AC XY: 30656 AN XY: 74328

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.422

Alfa AF: 0.421 Hom.: 14049

Bravo AF: 0.381

Asia WGS AF: 0.478 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.46
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3806933; hg19: chr5-110406742;