rs11466743

Positions:

• chr5-111073169-G-A

Variant summary

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

The ENST00000344895.4(TSLP):​c.216+237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 906,686 control chromosomes in the GnomAD database, including 115 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 0.018 (88 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (27 hom.)
• Consequence: TSLP ENST00000344895.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSLP	NM_033035.5	c.216+237G>A		intron_variant		ENST00000344895.4	NP_149024.1
TSLP	XM_047417846.1	c.186+237G>A		intron_variant			XP_047273802.1
TSLP	XM_047417847.1	c.54+237G>A		intron_variant			XP_047273803.1
TSLP	NR_045089.2	n.1638+237G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.216+237G>A		intron_variant		1	NM_033035.5	ENSP00000339804	P4
TSLP	ENST00000420978.6	c.216+237G>A		intron_variant		1		ENSP00000399099	A2

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2811 AN: 152236 Hom.: 87 Cov.: 33

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00166 AC: 1252 AN: 754332 Hom.: 27 AF XY: 0.00132 AC XY: 503 AN XY: 380290

Gnomad4 AFR exome AF: 0.0597

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000208

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000179

Gnomad4 OTH exome AF: 0.00351

GnomAD4 genome AF: 0.0185 AC: 2818 AN: 152354 Hom.: 88 Cov.: 33 AF XY: 0.0175 AC XY: 1307 AN XY: 74510

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0229 Hom.: 13

Bravo AF: 0.0202

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs11466743; hg19: chr5-110408867;