5-111073369-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000379706.4(TSLP):​c.-214C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000655 in 1,527,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: TSLP ENST00000379706.4 5_prime_UTR_premature_start_codon_gain
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSLP	ENST00000379706.4	TSL:1	c.-214C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000427827.1
	TSLP	ENST00000379706.4	TSL:1	c.-214C>T		5_prime_UTR	Exon 1 of 2	ENSP00000427827.1
	TSLP	ENST00000344895.4	TSL:1 MANE Select	c.217-142C>T		intron	N/A	ENSP00000339804.3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000436 AC: 6 AN: 1375708 Hom.: 0 Cov.: 34 AF XY: 0.00000296 AC XY: 2 AN XY: 675634

African (AFR) AF: 0.00 AC: 0 AN: 30928

American (AMR) AF: 0.00 AC: 0 AN: 32438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20920

East Asian (EAS) AF: 0.00 AC: 0 AN: 38672

South Asian (SAS) AF: 0.00 AC: 0 AN: 71772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4970

European-Non Finnish (NFE) AF: 0.00000560 AC: 6 AN: 1071972

Other (OTH) AF: 0.00 AC: 0 AN: 56842

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151990 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74232

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 928

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.96
PhyloP100		-3.0
PromoterAI		-0.066	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;