8-78746947-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000880.4(IL7):c.148-6865A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 412,962 control chromosomes in the GnomAD database, including 2,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (928 hom., cov: 32)
  • Exomes 𝑓: 0.077 (1204 hom.)
• Consequence: IL7 NM_000880.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.780

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-78746947-T-A is Benign according to our data. Variant chr8-78746947-T-A is described in ClinVar as [Benign]. Clinvar id is 2688314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7	NM_000880.4	c.148-6865A>T		intron_variant		ENST00000263851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7	ENST00000263851.9	c.148-6865A>T		intron_variant		1	NM_000880.4

Frequencies

GnomAD3 genomes AF: 0.0970 AC: 14759 AN: 152096 Hom.: 928 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0915

GnomAD4 exome AF: 0.0773 AC: 20150 AN: 260748 Hom.: 1204 Cov.: 0 AF XY: 0.0732 AC XY: 10952 AN XY: 149586

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.0495

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.0605

Gnomad4 NFE exome AF: 0.0638

Gnomad4 OTH exome AF: 0.0766

GnomAD4 genome AF: 0.0970 AC: 14767 AN: 152214 Hom.: 928 Cov.: 32 AF XY: 0.0978 AC XY: 7280 AN XY: 74418

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0643

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.0321 Hom.: 17

Bravo AF: 0.109

Asia WGS AF: 0.179 AC: 621 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.21
Dann	Benign	0.50

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: rs16906062; hg19: chr8-79659182; COSMIC: COSV55674991; COSMIC: COSV55674991;