dbSNP rs11466750: TSLP:c.*1122G>A (chr5-111077196-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033035.5(TSLP):c.*1122G>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 0.167 in 152,170 control chromosomes in the GnomAD database, including 2,303 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 0.17 ( 2303 hom., cov: 32)

Exomes 𝑓: 0.28 ( 0 hom. )

Consequence

TSLP
NM_033035.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.704

Publications

31 publications found

Variant links:

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]

TSLP links:

ENSG00000253613 (HGNC:):

ENSG00000253613 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSLP	NM_033035.5 link	c.*1122G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000344895.4	NP_149024.1	Q969D9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4 link	c.*1122G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_033035.5	ENSP00000339804.3		Q969D9-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25303

AN:

152032

Hom.:

2296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0685

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.154

GnomAD4 exome

AF:

0.278

AC:

AN:

Hom.:

Cov.:

AF XY:

0.313

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.166

AC:

25332

AN:

152152

Hom.:

2303

Cov.:

AF XY:

0.166

AC XY:

12344

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.227

AC:

9411

AN:

41478

American (AMR)

AF:

0.107

AC:

1643

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

366

AN:

3466

East Asian (EAS)

AF:

0.0686

AC:

356

AN:

5188

South Asian (SAS)

AF:

0.278

AC:

1339

AN:

4812

European-Finnish (FIN)

AF:

0.142

AC:

1505

AN:

10590

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10247

AN:

68000

Other (OTH)

AF:

0.154

AC:

325

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1039

2078

3118

4157

5196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.148

Hom.:

2265

Bravo

AF:

0.158

Asia WGS

AF:

0.179

AC:

622

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.61

(source)

DANN

Benign

0.73

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over