chr5-111073369-C-G

Position:

• chr5-111073369-C-G

Variant summary

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

The ENST00000379706.4(TSLP):​c.-214C>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 0.448 in 1,526,974 control chromosomes in the GnomAD database, including 156,238 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 0.45 (15453 hom., cov: 32)
  • Exomes 𝑓: 0.45 (140785 hom.)
• Consequence: TSLP ENST00000379706.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSLP	NM_033035.5	c.217-142C>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.-214C>G		5_prime_UTR_variant	1/2	1		ENSP00000427827.1
TSLP	ENST00000344895.4	c.217-142C>G		intron_variant		1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000420978.6	c.217-142C>G		intron_variant		1		ENSP00000399099.2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67798 AN: 151904 Hom.: 15448 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.448 AC: 615542 AN: 1374950 Hom.: 140785 Cov.: 34 AF XY: 0.454 AC XY: 306616 AN XY: 675190

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.665

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.446 AC: 67849 AN: 152024 Hom.: 15453 Cov.: 32 AF XY: 0.454 AC XY: 33708 AN XY: 74312

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.460

Alfa AF: 0.323 Hom.: 928

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2289277; hg19: chr5-110409067; COSMIC: COSV61291272; COSMIC: COSV61291272;