rs1187066798

Variant names:

• chr5-111075988-G-A
• rs1187066798
• NM_033035.5:c.394G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-111075988-G-A
• chr5-111075988-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033035.5(TSLP):​c.394G>A​(p.Val132Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSLP NM_033035.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0672065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSLP	NM_033035.5	c.394G>A	p.Val132Ile	missense_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.394G>A	p.Val132Ile	missense_variant	Exon 4 of 4	1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000420978.6	c.394G>A	p.Val132Ile	missense_variant	Exon 5 of 5	1		ENSP00000399099.2
TSLP	ENST00000379706.4	c.106G>A	p.Val36Ile	missense_variant	Exon 2 of 2	1		ENSP00000427827.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	.;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	.;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.36	N;N;N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.26	T;T;D
Polyphen		0.15	.;B;.
Vest4		0.093
MutPred		0.21		Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;
MVP		0.030
MPC		0.28
ClinPred		0.13	T
GERP RS		0.78
Varity_R		0.15
gMVP		0.070

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

Publications

LitVar

Other links and lift over

dbSNP: rs1187066798; hg19: chr5-110411686;