rs11466749

Variant names:

• chr5-111076887-A-G
• rs11466749
• NM_033035.5:c.*813A>G

Variant summary

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

The NM_033035.5(TSLP):​c.*813A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,134 control chromosomes in the GnomAD database, including 1,776 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 0.15 (1775 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: TSLP NM_033035.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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]

ENSG00000253613 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• 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 rank	MANE	Protein	UniProt
TSLP	NM_033035.5	c.*813A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000344895.4	NP_149024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.*813A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000379706.4	c.*813A>G		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000427827.1
TSLP	ENST00000420978.6	c.*813A>G		downstream_gene_variant		1		ENSP00000399099.2
ENSG00000253613	ENST00000507269.3	n.*34T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22430 AN: 152002 Hom.: 1774 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0682

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.148 AC: 22440 AN: 152120 Hom.: 1775 Cov.: 32 AF XY: 0.148 AC XY: 10998 AN XY: 74362

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.138

Alfa AF: 0.154 Hom.: 1931

Bravo AF: 0.132

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11466749; hg19: chr5-110412585;