Variant chr5-111073007-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033035.5(TSLP):c.216+75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,547,702 control chromosomes in the GnomAD database, including 75,872 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 0.31 ( 7639 hom., cov: 33)

Exomes 𝑓: 0.31 ( 68233 hom. )

Consequence

TSLP
NM_033035.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

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:

TSLP (HGNC:):

TSLP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TSLP	NM_033035.5 linkuse as main transcript	c.216+75C>T	intron_variant	ENST00000344895.4	NP_149024.1	Q969D9-1
TSLP	XM_047417846.1 linkuse as main transcript	c.186+75C>T	intron_variant		XP_047273802.1
TSLP	XM_047417847.1 linkuse as main transcript	c.54+75C>T	intron_variant		XP_047273803.1
TSLP	NR_045089.2 linkuse as main transcript	n.1638+75C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4 linkuse as main transcript	c.216+75C>T		intron_variant		1	NM_033035.5	ENSP00000339804.3		Q969D9-1
TSLP	ENST00000420978.6 linkuse as main transcript	c.216+75C>T		intron_variant		1		ENSP00000399099.2		A0A0C4DG43

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47549

AN:

152042

Hom.:

7632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.310

AC:

432223

AN:

1395542

Hom.:

68233

AF XY:

0.313

AC XY:

218135

AN XY:

697188

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.417

Gnomad4 ASJ exome

AF:

0.372

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.313

AC:

47588

AN:

152160

Hom.:

7639

Cov.:

AF XY:

0.319

AC XY:

23740

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.363

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.282

Hom.:

3023

Bravo

AF:

0.309

Asia WGS

AF:

0.320

AC:

1116

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.54

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over