rs104893894

chr5-35871070-C-Gchr5-35871070-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PM5 PP3_Strong

The NM_002185.5(IL7R):c.394C>G(p.Pro132Ala) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P132S) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47

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 Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr5-35871070-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 14843.Status of the report is reviewed_by_expert_panel, 3 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.394C>G	p.Pro132Ala	missense_variant	4/8	ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.394C>G	p.Pro132Ala	missense_variant	4/8	1	NM_002185.5	P1
IL7R	ENST00000506850.5	c.394C>G	p.Pro132Ala	missense_variant	4/6	2
IL7R	ENST00000514217.5	c.394C>G	p.Pro132Ala	missense_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.8	D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.64
MutPred		0.85		Gain of catalytic residue at P132 (P = 0.0903);Gain of catalytic residue at P132 (P = 0.0903);
MVP		0.99
MPC		0.11
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.97
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-35871172;