rs200150755

chr5-35874514-A-Cchr5-35874514-A-Gchr5-35874514-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002185.5(IL7R):c.772A>C(p.Ile258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I258F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30116683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.772A>C	p.Ile258Leu	missense_variant	6/8	ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.772A>C	p.Ile258Leu	missense_variant	6/8	1	NM_002185.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
Cadd	Benign	20
Dann	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.034
Eigen_PC	Benign	0.067
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.76	N
REVEL	Uncertain	0.60
Sift	Benign	0.096	T
Sift4G	Benign	0.10	T
Polyphen		0.45	B
Vest4		0.38
MutPred		0.35		Loss of catalytic residue at I258 (P = 0.0491);
MVP		0.97
MPC		0.019
ClinPred		0.35	T
GERP RS		3.3
Varity_R		0.13
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs200150755; hg19: chr5-35874616;