rs1898671

Positions:

• chr5-111072304-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033035.5(TSLP):​c.171+243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,004 control chromosomes in the GnomAD database, including 5,725 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 0.25 (5725 hom., cov: 32)
• Consequence: TSLP NM_033035.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSLP	NM_033035.5	c.171+243C>T		intron_variant		ENST00000344895.4	NP_149024.1
TSLP	XM_047417846.1	c.141+243C>T		intron_variant			XP_047273802.1
TSLP	XM_047417847.1	c.9+243C>T		intron_variant			XP_047273803.1
TSLP	NR_045089.2	n.1593+243C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.171+243C>T		intron_variant		1	NM_033035.5	ENSP00000339804	P4
TSLP	ENST00000420978.6	c.171+243C>T		intron_variant		1		ENSP00000399099	A2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37923 AN: 151888 Hom.: 5726 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.274

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 37928 AN: 152004 Hom.: 5725 Cov.: 32 AF XY: 0.242 AC XY: 17998 AN XY: 74304

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.0429

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.274

Alfa AF: 0.328 Hom.: 7947

Bravo AF: 0.249

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.64

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: rs1898671; hg19: chr5-110408002;