rs10073816

chr5-111077791-G-Achr5-111077791-G-T

Variant summary

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

The NM_033035.5(TSLP):c.*1717G>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 0.505 in 152,388 control chromosomes in the GnomAD database, including 20,050 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 0.51 (19988 hom., cov: 32)
  • Exomes 𝑓: 0.54 (62 hom.)
• Consequence: TSLP NM_033035.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSLP	NM_033035.5	c.*1717G>A		3_prime_UTR_variant	4/4	ENST00000344895.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSLP	ENST00000344895.4	c.*1717G>A		3_prime_UTR_variant	4/4	1	NM_033035.5	P4
TSLP	ENST00000379706.4	c.*1717G>A		3_prime_UTR_variant	2/2	1
	ENST00000507269.3	n.213-315C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76722 AN: 151838 Hom.: 19967 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.544 AC: 235 AN: 432 Hom.: 62 Cov.: 0 AF XY: 0.523 AC XY: 136 AN XY: 260

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.505 AC: 76796 AN: 151956 Hom.: 19988 Cov.: 32 AF XY: 0.511 AC XY: 37935 AN XY: 74274

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.497

Alfa AF: 0.421 Hom.: 3747

Bravo AF: 0.497

Asia WGS AF: 0.501 AC: 1737 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.61
Dann	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10073816; hg19: chr5-110413489;