rs2953475

Variant names:

• chr8-78725903-C-A
• rs2953475
• ENST00000519833.5:n.268-4463G>T

Variant summary

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

The ENST00000519833.5(IL7):​n.268-4463G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,704 control chromosomes in the GnomAD database, including 9,931 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 0.34 (9931 hom., cov: 32)
• Consequence: IL7 ENST00000519833.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7	XM_011517522.4	c.415-4463G>T		intron_variant	Intron 5 of 5		XP_011515824.1
IL7	XM_011517523.4	c.414+10571G>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.268-4463G>T		intron_variant	Intron 3 of 6	5
IL7	ENST00000523959.5	n.122-4463G>T		intron_variant	Intron 2 of 4	3
ENSG00000296852	ENST00000743040.1	n.339-25C>A		intron_variant	Intron 2 of 3
ENSG00000296852	ENST00000743041.1	n.215+1714C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50955 AN: 151586 Hom.: 9898 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.336 AC: 51042 AN: 151704 Hom.: 9931 Cov.: 32 AF XY: 0.334 AC XY: 24772 AN XY: 74118

African (AFR) AF: 0.534 AC: 22088 AN: 41370

American (AMR) AF: 0.265 AC: 4036 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1488 AN: 3462

East Asian (EAS) AF: 0.0966 AC: 499 AN: 5164

South Asian (SAS) AF: 0.242 AC: 1163 AN: 4810

European-Finnish (FIN) AF: 0.262 AC: 2762 AN: 10532

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.264 AC: 17922 AN: 67844

Other (OTH) AF: 0.355 AC: 747 AN: 2106

Alfa AF: 0.314 Hom.: 1062

Bravo AF: 0.341

Asia WGS AF: 0.231 AC: 804 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.20
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs2953475; hg19: chr8-79638138;