8-78792165-G-T

Variant names:

• chr8-78792165-G-T
• rs2583760
• NM_000880.4:c.147+5907C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000880.4(IL7):​c.147+5907C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,070 control chromosomes in the GnomAD database, including 24 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 0.017 (24 hom., cov: 32)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 6 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=-0.95).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0168 (2551/152070) while in subpopulation SAS AF = 0.0193 (93/4812). AF 95% confidence interval is 0.0175. There are 24 homozygotes in GnomAd4. There are 1303 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7	NM_000880.4	c.147+5907C>A		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.147+5907C>A		intron_variant	Intron 2 of 5	1	NM_000880.4	ENSP00000263851.4

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2550 AN: 151952 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0221

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

GnomAD4 genome AF: 0.0168 AC: 2551 AN: 152070 Hom.: 24 Cov.: 32 AF XY: 0.0175 AC XY: 1303 AN XY: 74322

African (AFR) AF: 0.0113 AC: 470 AN: 41494

American (AMR) AF: 0.0140 AC: 214 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3468

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5164

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4812

European-Finnish (FIN) AF: 0.0273 AC: 289 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0184 AC: 1249 AN: 67976

Other (OTH) AF: 0.0218 AC: 46 AN: 2108

Alfa AF: 0.00493 Hom.: 2

Bravo AF: 0.0158

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.33
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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: rs2583760; hg19: chr8-79704400;