5-35856997-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002185.5(IL7R):c.20C>T(p.Thr7Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1646012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.20C>T	p.Thr7Ile	missense_variant	1/8	ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.20C>T	p.Thr7Ile	missense_variant	1/8	1	NM_002185.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.20C>T (p.T7I) alteration is located in exon 1 (coding exon 1) of the IL7R gene. This alteration results from a C to T substitution at nucleotide position 20, causing the threonine (T) at amino acid position 7 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	16
Dann	Uncertain	0.98
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.57	T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.021	D;D;T;T;D
Sift4G	Uncertain	0.035	D;D;T;D;D
Polyphen		0.031	.;.;B;.;.
Vest4		0.17, 0.34, 0.16
MutPred		0.30		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.90
MPC		0.016
ClinPred		0.25	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.42

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: rs1162451134; hg19: chr5-35857099;