rs2228141

chr5-35871171-C-Achr5-35871171-C-Gchr5-35871171-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002185.5(IL7R):c.495C>A(p.His165Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H165H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.495C>A	p.His165Gln	missense_variant	4/8	ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.495C>A	p.His165Gln	missense_variant	4/8	1	NM_002185.5	P1
IL7R	ENST00000506850.5	c.495C>A	p.His165Gln	missense_variant	4/6	2
IL7R	ENST00000514217.5	c.495C>A	p.His165Gln	missense_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0060	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.79
MutPred		0.71		Gain of MoRF binding (P = 0.09);Gain of MoRF binding (P = 0.09);
MVP		0.89
MPC		0.11
ClinPred		0.98	D
GERP RS		-2.7
Varity_R		0.84
gMVP		0.66

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: rs2228141; hg19: chr5-35871273;