rs17505589

Variant names:

• chr8-78777400-C-T
• rs17505589
• NM_000880.4:c.147+20672G>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+20672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,028 control chromosomes in the GnomAD database, including 577 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 0.073 (577 hom., cov: 32)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0996 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7	NM_000880.4	MANE Select	c.147+20672G>A		intron	N/A	NP_000871.1
	IL7	NM_001199887.2		c.147+20672G>A		intron	N/A	NP_001186816.1
	IL7	NM_001199886.2		c.147+20672G>A		intron	N/A	NP_001186815.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7	ENST00000263851.9	TSL:1 MANE Select	c.147+20672G>A		intron	N/A	ENSP00000263851.4
	IL7	ENST00000518982.5	TSL:1	n.147+20672G>A		intron	N/A	ENSP00000430272.1
	IL7	ENST00000520317.1	TSL:1	n.91+20728G>A		intron	N/A	ENSP00000427800.1

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11141 AN: 151910 Hom.: 578 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.0732 AC: 11133 AN: 152028 Hom.: 577 Cov.: 32 AF XY: 0.0731 AC XY: 5433 AN XY: 74334

African (AFR) AF: 0.0199 AC: 828 AN: 41526

American (AMR) AF: 0.0876 AC: 1335 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5158

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4818

European-Finnish (FIN) AF: 0.0953 AC: 1010 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6899 AN: 67918

Other (OTH) AF: 0.106 AC: 223 AN: 2108

Alfa AF: 0.0944 Hom.: 385

Bravo AF: 0.0701

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.57
PhyloP100		-1.0
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: rs17505589; hg19: chr8-79689635;