rs2583764

Variant names:

• chr8-78751565-A-G
• rs2583764
• NM_000880.4:c.148-11483T>C

Variant summary

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

The NM_000880.4(IL7):​c.148-11483T>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
• Publications: 10 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 = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000880.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7	NM_000880.4	MANE Select	c.148-11483T>C		intron	N/A	NP_000871.1
	IL7	NM_001199887.2		c.148-11483T>C		intron	N/A	NP_001186816.1
	IL7	NM_001199886.2		c.148-11483T>C		intron	N/A	NP_001186815.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7	ENST00000263851.9	TSL:1 MANE Select	c.148-11483T>C		intron	N/A	ENSP00000263851.4
	IL7	ENST00000518982.5	TSL:1	n.148-4469T>C		intron	N/A	ENSP00000430272.1
	IL7	ENST00000520317.1	TSL:1	n.92-11483T>C		intron	N/A	ENSP00000427800.1

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

African (AFR) AF: 0.543 AC: 22528 AN: 41450

American (AMR) AF: 0.255 AC: 3905 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1601 AN: 5162

South Asian (SAS) AF: 0.153 AC: 736 AN: 4812

European-Finnish (FIN) AF: 0.173 AC: 1833 AN: 10582

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11100 AN: 67982

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.254 Hom.: 1211

Bravo AF: 0.304

Asia WGS AF: 0.279 AC: 971 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-2.4
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: rs2583764; hg19: chr8-79663800;