ENST00000743040.1:n.515C>T

Variant names:

• chr8-78729671-C-T
• rs1036751
• ENST00000743040.1:n.515C>T

Variant summary

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

The ENST00000743040.1(ENSG00000296852):​n.515C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,738 control chromosomes in the GnomAD database, including 3,954 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 0.22 (3954 hom., cov: 32)
• Consequence: ENSG00000296852 ENST00000743040.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 2 publications found

Genes affected

ENSG00000296852 (HGNC:):

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7	XM_011517522.4	c.414+6803G>A		intron_variant	Intron 5 of 5		XP_011515824.1
IL7	XM_011517523.4	c.414+6803G>A		intron_variant	Intron 5 of 5		XP_011515825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296852	ENST00000743040.1	n.515C>T		non_coding_transcript_exon_variant	Exon 4 of 4
ENSG00000296852	ENST00000743041.1	n.298C>T		non_coding_transcript_exon_variant	Exon 2 of 2
IL7	ENST00000519833.5	n.267+6803G>A		intron_variant	Intron 3 of 6	5
IL7	ENST00000523959.5	n.121+6803G>A		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32965 AN: 151620 Hom.: 3944 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.218 AC: 33008 AN: 151738 Hom.: 3954 Cov.: 32 AF XY: 0.216 AC XY: 16008 AN XY: 74146

African (AFR) AF: 0.297 AC: 12275 AN: 41384

American (AMR) AF: 0.180 AC: 2734 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1177 AN: 3462

East Asian (EAS) AF: 0.0934 AC: 482 AN: 5160

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1626 AN: 10576

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12900 AN: 67834

Other (OTH) AF: 0.251 AC: 529 AN: 2106

Alfa AF: 0.200 Hom.: 949

Bravo AF: 0.221

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		0.060

Splicing

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

Other links and lift over

dbSNP: rs1036751; hg19: chr8-79641906;