rs1441438

Variant names:

• chr8-78729534-G-A
• rs1441438
• ENST00000519833.5:n.267+6940C>T

Variant summary

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

The ENST00000519833.5(IL7):​n.267+6940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,736 control chromosomes in the GnomAD database, including 8,404 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 0.32 (8404 hom., cov: 32)
• Consequence: IL7 ENST00000519833.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 14 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

ENSG00000296852 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7	XM_011517522.4	c.414+6940C>T		intron_variant	Intron 5 of 5		XP_011515824.1
IL7	XM_011517523.4	c.414+6940C>T		intron_variant	Intron 5 of 5		XP_011515825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7	ENST00000519833.5	n.267+6940C>T		intron_variant	Intron 3 of 6	5
IL7	ENST00000523959.5	n.121+6940C>T		intron_variant	Intron 2 of 4	3
ENSG00000296852	ENST00000743040.1	n.433-55G>A		intron_variant	Intron 3 of 3
ENSG00000296852	ENST00000743041.1	n.216-55G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47800 AN: 151618 Hom.: 8386 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.315 AC: 47859 AN: 151736 Hom.: 8404 Cov.: 32 AF XY: 0.313 AC XY: 23247 AN XY: 74170

African (AFR) AF: 0.467 AC: 19349 AN: 41404

American (AMR) AF: 0.250 AC: 3794 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3466

East Asian (EAS) AF: 0.0941 AC: 486 AN: 5164

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4820

European-Finnish (FIN) AF: 0.262 AC: 2769 AN: 10556

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17795 AN: 67828

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.282 Hom.: 12080

Bravo AF: 0.318

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.32
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs1441438; hg19: chr8-79641769;