8-78732729-T-C

Variant names:

• chr8-78732729-T-C
• rs2583759
• ENST00000519833.5:n.267+3745A>G

Variant summary

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

The ENST00000519833.5(IL7):​n.267+3745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,072 control chromosomes in the GnomAD database, including 3,774 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 0.21 (3774 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL7 ENST00000519833.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519833.5. 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.*984A>G		downstream_gene	N/A	NP_000871.1
	IL7	NM_001199887.2		c.*984A>G		downstream_gene	N/A	NP_001186816.1
	IL7	NM_001199886.2		c.*984A>G		downstream_gene	N/A	NP_001186815.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7	ENST00000519833.5	TSL:5	n.267+3745A>G		intron	N/A
	IL7	ENST00000523959.5	TSL:3	n.121+3745A>G		intron	N/A
	IL7	ENST00000263851.9	TSL:1 MANE Select	c.*984A>G		downstream_gene	N/A	ENSP00000263851.4

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32365 AN: 151954 Hom.: 3766 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.0935

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.247

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.213 AC: 32389 AN: 152072 Hom.: 3774 Cov.: 32 AF XY: 0.211 AC XY: 15717 AN XY: 74338

African (AFR) AF: 0.283 AC: 11723 AN: 41466

American (AMR) AF: 0.177 AC: 2701 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3466

East Asian (EAS) AF: 0.0935 AC: 485 AN: 5186

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1623 AN: 10604

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.190 AC: 12913 AN: 67958

Other (OTH) AF: 0.248 AC: 524 AN: 2112

Alfa AF: 0.205 Hom.: 572

Bravo AF: 0.216

Asia WGS AF: 0.185 AC: 642 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.82
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2583759; hg19: chr8-79644964;