rs2583763

Positions:

• chr8-78751173-G-A

Variant summary

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

The NM_000880.4(IL7):​c.148-11091C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 150,900 control chromosomes in the GnomAD database, including 3,825 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 0.19 (3825 hom., cov: 31)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL7	NM_000880.4	c.148-11091C>T		intron_variant		ENST00000263851.9	NP_000871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL7	ENST00000263851.9	c.148-11091C>T		intron_variant		1	NM_000880.4	ENSP00000263851

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28703 AN: 150788 Hom.: 3795 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.191 AC: 28791 AN: 150900 Hom.: 3825 Cov.: 31 AF XY: 0.192 AC XY: 14141 AN XY: 73728

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0948

Gnomad4 NFE AF: 0.0998

Gnomad4 OTH AF: 0.184

Alfa AF: 0.119 Hom.: 1282

Bravo AF: 0.211

Asia WGS AF: 0.261 AC: 906 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.1
DANN	Benign	0.69

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: rs2583763; hg19: chr8-79663408;