5-111073007-C-T

Variant names:

• chr5-111073007-C-T
• rs11466741
• NM_033035.5:c.216+75C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 22 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSLP	NM_033035.5	c.216+75C>T		intron_variant	Intron 2 of 3	ENST00000344895.4	NP_149024.1
TSLP	NR_045089.2	n.1638+75C>T		intron_variant	Intron 3 of 4
TSLP	XM_047417846.1	c.186+75C>T		intron_variant	Intron 3 of 4		XP_047273802.1
TSLP	XM_047417847.1	c.54+75C>T		intron_variant	Intron 3 of 4		XP_047273803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSLP	ENST00000344895.4	c.216+75C>T		intron_variant	Intron 2 of 3	1	NM_033035.5	ENSP00000339804.3
TSLP	ENST00000420978.6	c.216+75C>T		intron_variant	Intron 3 of 4	1		ENSP00000399099.2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47549 AN: 152042 Hom.: 7632 Cov.: 33

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

African (AFR) AF: 0.306 AC: 9799 AN: 32058

American (AMR) AF: 0.417 AC: 17931 AN: 42962

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9531 AN: 25606

East Asian (EAS) AF: 0.265 AC: 10409 AN: 39306

South Asian (SAS) AF: 0.399 AC: 33660 AN: 84374

European-Finnish (FIN) AF: 0.381 AC: 20242 AN: 53104

Middle Eastern (MID) AF: 0.423 AC: 2381 AN: 5634

European-Non Finnish (NFE) AF: 0.294 AC: 309729 AN: 1054298

Other (OTH) AF: 0.319 AC: 18541 AN: 58200

GnomAD4 genome AF: 0.313 AC: 47588 AN: 152160 Hom.: 7639 Cov.: 33 AF XY: 0.319 AC XY: 23740 AN XY: 74384

African (AFR) AF: 0.301 AC: 12512 AN: 41522

American (AMR) AF: 0.352 AC: 5377 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1856 AN: 4818

European-Finnish (FIN) AF: 0.396 AC: 4195 AN: 10586

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19970 AN: 67986

Other (OTH) AF: 0.326 AC: 688 AN: 2112

Alfa AF: 0.295 Hom.: 5278

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
PhyloP100		-2.8
PromoterAI		-0.086	Neutral
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: rs11466741; hg19: chr5-110408705; COSMIC: COSV61291850; COSMIC: COSV61291850;