chr8-78741910-A-G

Position:

• chr8-78741910-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263851.9(IL7):​c.148-1828T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,050 control chromosomes in the GnomAD database, including 17,023 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 0.44 (17023 hom., cov: 32)
• Consequence: IL7 ENST00000263851.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL7	NM_000880.4	c.148-1828T>C		intron_variant		ENST00000263851.9	NP_000871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL7	ENST00000263851.9	c.148-1828T>C		intron_variant		1	NM_000880.4	ENSP00000263851

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67221 AN: 151932 Hom.: 16981 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.443 AC: 67317 AN: 152050 Hom.: 17023 Cov.: 32 AF XY: 0.441 AC XY: 32790 AN XY: 74324

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.454

Alfa AF: 0.359 Hom.: 21519

Bravo AF: 0.461

Asia WGS AF: 0.413 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.31
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs6993386; hg19: chr8-79654145;