rs11466750

Positions:

• chr5-111077196-G-A

Variant summary

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

The NM_033035.5(TSLP):​c.*1122G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,170 control chromosomes in the GnomAD database, including 2,303 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 0.17 (2303 hom., cov: 32)
  • Exomes 𝑓: 0.28 (0 hom.)
• Consequence: TSLP NM_033035.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSLP	NM_033035.5	c.*1122G>A		3_prime_UTR_variant	4/4	ENST00000344895.4	NP_149024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.*1122G>A		3_prime_UTR_variant	4/4	1	NM_033035.5	ENSP00000339804	P4
TSLP	ENST00000379706.4	c.*1122G>A		3_prime_UTR_variant	2/2	1		ENSP00000427827
	ENST00000507269.3	n.318-151C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25303 AN: 152032 Hom.: 2296 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.278 AC: 5 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.313 AC XY: 5 AN XY: 16

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.166 AC: 25332 AN: 152152 Hom.: 2303 Cov.: 32 AF XY: 0.166 AC XY: 12344 AN XY: 74384

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.154

Alfa AF: 0.146 Hom.: 1707

Bravo AF: 0.158

Asia WGS AF: 0.179 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11466750; hg19: chr5-110412894;