rs10073816

Variant names:

• chr5-111077791-G-A
• rs10073816
• NM_033035.5:c.*1717G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-111077791-G-A
• chr5-111077791-G-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.*1717G>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 0.505 in 152,388 control chromosomes in the GnomAD database, including 20,050 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 0.51 (19988 hom., cov: 32)
  • Exomes 𝑓: 0.54 (62 hom.)
• Consequence: TSLP NM_033035.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 25 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]

ENSG00000253613 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033035.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSLP	NM_033035.5	MANE Select	c.*1717G>A		3_prime_UTR	Exon 4 of 4	NP_149024.1
	TSLP	NR_045089.2		n.3619G>A		non_coding_transcript_exon	Exon 5 of 5
	TSLP	NM_138551.5		c.*1717G>A		3_prime_UTR	Exon 2 of 2	NP_612561.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSLP	ENST00000344895.4	TSL:1 MANE Select	c.*1717G>A		3_prime_UTR	Exon 4 of 4	ENSP00000339804.3
	TSLP	ENST00000379706.4	TSL:1	c.*1717G>A		3_prime_UTR	Exon 2 of 2	ENSP00000427827.1
	ENSG00000253613	ENST00000507269.3	TSL:5	n.213-315C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76722 AN: 151838 Hom.: 19967 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.544 AC: 235 AN: 432 Hom.: 62 Cov.: 0 AF XY: 0.523 AC XY: 136 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.538 AC: 229 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.505 AC: 76796 AN: 151956 Hom.: 19988 Cov.: 32 AF XY: 0.511 AC XY: 37935 AN XY: 74274

African (AFR) AF: 0.618 AC: 25631 AN: 41460

American (AMR) AF: 0.468 AC: 7149 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1627 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1732 AN: 5160

South Asian (SAS) AF: 0.666 AC: 3205 AN: 4812

European-Finnish (FIN) AF: 0.539 AC: 5664 AN: 10512

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30240 AN: 67952

Other (OTH) AF: 0.497 AC: 1049 AN: 2112

Alfa AF: 0.433 Hom.: 5015

Bravo AF: 0.497

Asia WGS AF: 0.501 AC: 1737 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.61
DANN	Benign	0.21
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10073816; hg19: chr5-110413489;