rs10062929

Variant names:

• chr5-111072481-C-A
• rs10062929
• NM_033035.5:c.172-407C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033035.5(TSLP):​c.172-407C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,172 control chromosomes in the GnomAD database, including 1,364 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 0.13 (1364 hom., cov: 32)
• Consequence: TSLP NM_033035.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSLP	NM_033035.5	c.172-407C>A		intron_variant	Intron 1 of 3	ENST00000344895.4	NP_149024.1
TSLP	NR_045089.2	n.1594-407C>A		intron_variant	Intron 2 of 4
TSLP	XM_047417846.1	c.142-407C>A		intron_variant	Intron 2 of 4		XP_047273802.1
TSLP	XM_047417847.1	c.10-407C>A		intron_variant	Intron 2 of 4		XP_047273803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.172-407C>A		intron_variant	Intron 1 of 3	1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000420978.6	c.172-407C>A		intron_variant	Intron 2 of 4	1		ENSP00000399099.2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19535 AN: 152054 Hom.: 1365 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0612

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.128 AC: 19538 AN: 152172 Hom.: 1364 Cov.: 32 AF XY: 0.129 AC XY: 9615 AN XY: 74394

African (AFR) AF: 0.0990 AC: 4111 AN: 41514

American (AMR) AF: 0.0888 AC: 1359 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3472

East Asian (EAS) AF: 0.0613 AC: 318 AN: 5184

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4814

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10572

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10157 AN: 67996

Other (OTH) AF: 0.125 AC: 264 AN: 2116

Alfa AF: 0.139 Hom.: 1059

Bravo AF: 0.114

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.070
DANN	Benign	0.28
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10062929; hg19: chr5-110408179;