5-35871109-G-T

Variant names:

• chr5-35871109-G-T
• rs201790329
• NM_002185.5:c.433G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002185.5(IL7R):​c.433G>T​(p.Asp145Tyr) 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. D145N) 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: 5.70

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.433G>T	p.Asp145Tyr	missense_variant	Exon 4 of 8	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.433G>T	p.Asp145Tyr	missense_variant	Exon 4 of 8	1	NM_002185.5	ENSP00000306157.3
IL7R	ENST00000506850.5	c.433G>T	p.Asp145Tyr	missense_variant	Exon 4 of 6	2		ENSP00000421207.1
IL7R	ENST00000514217.5	n.433G>T		non_coding_transcript_exon_variant	Exon 4 of 6	2		ENSP00000427688.1

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	0.89
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		5.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.67
MutPred		0.62		Gain of phosphorylation at D145 (P = 0.0977);Gain of phosphorylation at D145 (P = 0.0977);
MVP		0.87
MPC		0.11
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.87
gMVP		0.55
Mutation Taster		=25/75	disease causing

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

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Other links and lift over

dbSNP: rs201790329; hg19: chr5-35871211;