rs11567714

Variant names:

• chr5-35862883-C-T
• rs11567714
• NM_002185.5:c.221+1893C>T

Variant summary

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

The NM_002185.5(IL7R):​c.221+1893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 152,158 control chromosomes in the GnomAD database, including 614 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 0.077 (614 hom., cov: 32)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 6 publications found

Genes affected

IL7R (HGNC:6024): (interleukin 7 receptor) The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found. [provided by RefSeq, Dec 2015]

IL7R Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.221+1893C>T		intron_variant	Intron 2 of 7	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.221+1893C>T		intron_variant	Intron 2 of 7	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11780 AN: 152040 Hom.: 613 Cov.: 32

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.0774 AC: 11784 AN: 152158 Hom.: 614 Cov.: 32 AF XY: 0.0759 AC XY: 5647 AN XY: 74386

African (AFR) AF: 0.0207 AC: 859 AN: 41538

American (AMR) AF: 0.0767 AC: 1171 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0565 AC: 272 AN: 4812

European-Finnish (FIN) AF: 0.0804 AC: 852 AN: 10592

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7719 AN: 67988

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0915 Hom.: 173

Bravo AF: 0.0749

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.3
DANN	Benign	0.86
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11567714; hg19: chr5-35862985;