5-111073369-C-G

Variant names:

• chr5-111073369-C-G
• rs2289277
• ENST00000379706.4:c.-214C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379706.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSLP	NM_033035.5	MANE Select	c.217-142C>G		intron	N/A	NP_149024.1	Q969D9-1
	TSLP	NR_045089.2		n.1639-142C>G		intron	N/A
	TSLP	NM_138551.5		c.-214C>G		upstream_gene	N/A	NP_612561.2	Q969D9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSLP	ENST00000379706.4	TSL:1	c.-214C>G		5_prime_UTR	Exon 1 of 2	ENSP00000427827.1	Q969D9-2
	TSLP	ENST00000344895.4	TSL:1 MANE Select	c.217-142C>G		intron	N/A	ENSP00000339804.3	Q969D9-1
	TSLP	ENST00000420978.6	TSL:1	c.217-142C>G		intron	N/A	ENSP00000399099.2	A0A0C4DG43

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

African (AFR) AF: 0.424 AC: 13098 AN: 30906

American (AMR) AF: 0.476 AC: 15402 AN: 32374

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 9770 AN: 20904

East Asian (EAS) AF: 0.318 AC: 12277 AN: 38608

South Asian (SAS) AF: 0.665 AC: 47670 AN: 71694

European-Finnish (FIN) AF: 0.516 AC: 24324 AN: 47114

Middle Eastern (MID) AF: 0.567 AC: 2813 AN: 4958

European-Non Finnish (NFE) AF: 0.433 AC: 464250 AN: 1071586

Other (OTH) AF: 0.457 AC: 25938 AN: 56806

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

African (AFR) AF: 0.415 AC: 17230 AN: 41472

American (AMR) AF: 0.443 AC: 6772 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1618 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1737 AN: 5176

South Asian (SAS) AF: 0.665 AC: 3207 AN: 4824

European-Finnish (FIN) AF: 0.537 AC: 5667 AN: 10544

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30157 AN: 67942

Other (OTH) AF: 0.460 AC: 973 AN: 2114

Alfa AF: 0.323 Hom.: 928

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.49
PhyloP100		-3.0
PromoterAI		0.13	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289277; hg19: chr5-110409067; COSMIC: COSV61291272; COSMIC: COSV61291272;