Genetic Variant ENST00000420978.6:c.-1507A>G (chr5-111069977-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000420978.6(TSLP):c.-1507A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,016 control chromosomes in the GnomAD database, including 20,344 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 ( 20337 hom., cov: 31)

Exomes 𝑓: 0.67 ( 7 hom. )

Consequence

TSLP
ENST00000420978.6 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.837

Publications

64 publications found

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420978.6. 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	NR_045089.2		n.-85A>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSLP	ENST00000420978.6	TSL:1	c.-1507A>G		upstream_gene	N/A	ENSP00000399099.2

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77278

AN:

151868

Hom.:

20316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.626

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

AF XY:

0.714

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.636

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.509

AC:

77354

AN:

151986

Hom.:

20337

Cov.:

AF XY:

0.514

AC XY:

38173

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.626

AC:

25961

AN:

41440

American (AMR)

AF:

0.470

AC:

7190

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

1627

AN:

3464

East Asian (EAS)

AF:

0.336

AC:

1730

AN:

5156

South Asian (SAS)

AF:

0.671

AC:

3232

AN:

4816

European-Finnish (FIN)

AF:

0.538

AC:

5678

AN:

10548

Middle Eastern (MID)

AF:

0.623

AC:

182

AN:

292

European-Non Finnish (NFE)

AF:

0.447

AC:

30369

AN:

67956

Other (OTH)

AF:

0.506

AC:

1070

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1898

3797

5695

7594

9492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.463

Hom.:

78705

Bravo

AF:

0.500

Asia WGS

AF:

0.511

AC:

1781

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.6

(source)

DANN

Benign

0.73

PhyloP100

-0.84

PromoterAI

0.052

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over