rs2583764

Positions:

• chr8-78751565-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000880.4(IL7):​c.148-11483T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,070 control chromosomes in the GnomAD database, including 8,261 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 (8261 hom., cov: 32)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7	NM_000880.4	c.148-11483T>C		intron_variant		ENST00000263851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7	ENST00000263851.9	c.148-11483T>C		intron_variant		1	NM_000880.4

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43007 AN: 151952 Hom.: 8220 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.283 AC: 43110 AN: 152070 Hom.: 8261 Cov.: 32 AF XY: 0.284 AC XY: 21103 AN XY: 74354

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.267

Alfa AF: 0.248 Hom.: 1117

Bravo AF: 0.304

Asia WGS AF: 0.279 AC: 971 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	0.27
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2583764; hg19: chr8-79663800;