chr8-78736822-G-C

Variant names:

• chr8-78736822-G-C
• rs894221
• NM_000880.4:c.361-295C>G

Variant summary

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

The NM_000880.4(IL7):​c.361-295C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,906 control chromosomes in the GnomAD database, including 8,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.32 (8416 hom., cov: 32)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 12 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 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.361-295C>G		intron	N/A	NP_000871.1	P13232-1
	IL7	NM_001199887.2		c.360+1682C>G		intron	N/A	NP_001186816.1	A0A0A0MTG5
	IL7	NM_001199886.2		c.229-295C>G		intron	N/A	NP_001186815.1	P13232-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7	ENST00000263851.9	TSL:1 MANE Select	c.361-295C>G		intron	N/A	ENSP00000263851.4	P13232-1
	IL7	ENST00000518982.5	TSL:1	n.*348-295C>G		intron	N/A	ENSP00000430272.1	Q5FBY3
	IL7	ENST00000520317.1	TSL:1	n.*191-295C>G		intron	N/A	ENSP00000427800.1	Q5FBY6

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47872 AN: 151788 Hom.: 8399 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.316 AC: 47930 AN: 151906 Hom.: 8416 Cov.: 32 AF XY: 0.313 AC XY: 23272 AN XY: 74248

African (AFR) AF: 0.466 AC: 19303 AN: 41436

American (AMR) AF: 0.251 AC: 3837 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1524 AN: 3460

East Asian (EAS) AF: 0.0941 AC: 487 AN: 5176

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4818

European-Finnish (FIN) AF: 0.262 AC: 2769 AN: 10570

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17828 AN: 67872

Other (OTH) AF: 0.336 AC: 708 AN: 2110

Alfa AF: 0.149 Hom.: 246

Bravo AF: 0.318

Asia WGS AF: 0.206 AC: 716 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.63
DANN	Benign	0.78
PhyloP100		-0.60
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: rs894221; hg19: chr8-79649057; COSMIC: COSV55678437;