dbSNP rs587778404: IL7R:p.Pro197Gln (chr5-35873532-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002185.5(IL7R):c.590C>A(p.Pro197Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P197L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

IL7R
NM_002185.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.177

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

immunodeficiency 104
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
Omenn syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IL7R links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.379031).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002185.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL7R	NM_002185.5	MANE Select	c.590C>A	p.Pro197Gln	missense	Exon 5 of 8	NP_002176.2
IL7R	NM_001437964.1		c.590C>A	p.Pro197Gln	missense	Exon 5 of 7	NP_001424893.1
IL7R	NM_001410734.1		c.590C>A	p.Pro197Gln	missense	Exon 5 of 7	NP_001397663.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL7R	ENST00000303115.8	TSL:1 MANE Select	c.590C>A	p.Pro197Gln	missense	Exon 5 of 8	ENSP00000306157.3
IL7R	ENST00000877114.1		c.590C>A	p.Pro197Gln	missense	Exon 5 of 7	ENSP00000547173.1
IL7R	ENST00000506850.5	TSL:2	c.590C>A	p.Pro197Gln	missense	Exon 5 of 6	ENSP00000421207.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 104 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.34

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.71

M_CAP

Benign

0.046

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.3

PhyloP100

0.18

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.42

Sift

Benign

0.047

Sift4G

Benign

0.066

Polyphen

0.98

Vest4

0.25

MutPred

0.65

Gain of solvent accessibility (P = 0.0202)

MVP

0.85

MPC

0.089

ClinPred

0.89

GERP RS

4.1

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.26

gMVP

0.41

Mutation Taster

=92/8

polymorphism

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over