rs587778403

Positions:

• chr5-35871114-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002185.5(IL7R):​c.438T>A​(p.Phe146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.04

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL7R	NM_002185.5	c.438T>A	p.Phe146Leu	missense_variant	4/8	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.438T>A	p.Phe146Leu	missense_variant	4/8	1	NM_002185.5	ENSP00000306157.3
IL7R	ENST00000506850.5	c.438T>A	p.Phe146Leu	missense_variant	4/6	2		ENSP00000421207.1
IL7R	ENST00000514217.5	n.438T>A		non_coding_transcript_exon_variant	4/6	2		ENSP00000427688.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.024	D;T
Sift4G	Benign	0.097	T;D
Polyphen		1.0	D;.
Vest4		0.58
MutPred		0.60		Loss of catalytic residue at F146 (P = 0.0582);Loss of catalytic residue at F146 (P = 0.0582);
MVP		0.77
MPC		0.11
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.72
gMVP		0.48

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: rs587778403; hg19: chr5-35871216;