rs2583762

Variant names:

• chr8-78785248-A-T
• rs2583762
• NM_000880.4:c.147+12824T>A

Variant summary

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

The NM_000880.4(IL7):​c.147+12824T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,904 control chromosomes in the GnomAD database, including 7,978 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 0.28 (7978 hom., cov: 32)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 11 publications found

Genes affected

IL7 (HGNC:6023): (interleukin 7) The protein encoded by this gene is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. IL7 is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. IL7 plays an essential role in lymphoid cell survival, and in the maintenance of naive and memory T cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their presence in normal tissues has not been confirmed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be a potent inducer of proinflammatory cytokines and chemokines which may defend against the infection, but may also mediate destructive lung injury. Elevated serum IL7 levels, together with several other circulating cytokines and chemokines, has been found to be associated with the severity of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Jul 2020]

IL7 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epidermodysplasia verruciformis, susceptibility to, 5

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7	NM_000880.4	c.147+12824T>A		intron_variant	Intron 2 of 5	ENST00000263851.9	NP_000871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7	ENST00000263851.9	c.147+12824T>A		intron_variant	Intron 2 of 5	1	NM_000880.4	ENSP00000263851.4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42469 AN: 151784 Hom.: 7950 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.280 AC: 42555 AN: 151904 Hom.: 7978 Cov.: 32 AF XY: 0.281 AC XY: 20834 AN XY: 74216

African (AFR) AF: 0.531 AC: 21972 AN: 41412

American (AMR) AF: 0.253 AC: 3854 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1604 AN: 5130

South Asian (SAS) AF: 0.153 AC: 738 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1842 AN: 10552

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11145 AN: 67970

Other (OTH) AF: 0.265 AC: 559 AN: 2106

Alfa AF: 0.235 Hom.: 706

Bravo AF: 0.300

Asia WGS AF: 0.277 AC: 964 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.34
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: rs2583762; hg19: chr8-79697483;