chr8-78751173-G-A

Variant names:

• chr8-78751173-G-A
• rs2583763
• NM_000880.4:c.148-11091C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-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 rank	MANE	Protein	UniProt
IL7	NM_000880.4	c.148-11091C>T		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.148-11091C>T		intron_variant	Intron 2 of 5	1	NM_000880.4	ENSP00000263851.4

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

African (AFR) AF: 0.367 AC: 15085 AN: 41102

American (AMR) AF: 0.193 AC: 2933 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3468

East Asian (EAS) AF: 0.308 AC: 1581 AN: 5138

South Asian (SAS) AF: 0.131 AC: 631 AN: 4802

European-Finnish (FIN) AF: 0.0948 AC: 958 AN: 10104

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0998 AC: 6766 AN: 67802

Other (OTH) AF: 0.184 AC: 387 AN: 2098

Alfa AF: 0.123 Hom.: 1752

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
PhyloP100		-0.071
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: rs2583763; hg19: chr8-79663408;