rs201216012

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BA1BS2_Supporting

This summary comes from the ClinGen Evidence Repository: The c.1092T>G (NM_002185.5) variant in IL7R is a missense variant predicted to cause the substitution of Aspartic Acid by Glutamic Acid at amino acid 364 (p.Asp364Glu).The filtering allele frequency (the lower threshold of the 95% CI of 1584/91068 alleles) of the c.1092T>G variant in IL7R is 0.01668 for South Asian chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1, and therefore meets this criterion (BA1). Additionally, 35 adult homozygous occurrences are described in gnomAD (BS2_Supporting).In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1) LINK:https://erepo.genome.network/evrepo/ui/classification/CA160129/MONDO:0012163/119

Frequency

Genomes: 𝑓 0.00051 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

IL7R
NM_002185.5 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:3O:1

Conservation

PhyloP100: -1.75

Publications

7 publications found

Variant links:

COSMIC-nc: COSV57405437

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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

Specifications for IL7R are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BS2

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

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.1092T>G	p.Asp364Glu	missense	Exon 8 of 8	NP_002176.2
IL7R	NM_001437964.1		c.*590T>G		3_prime_UTR	Exon 7 of 7	NP_001424893.1
IL7R	NM_001410734.1		c.*209T>G		3_prime_UTR	Exon 7 of 7	NP_001397663.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL7R	ENST00000303115.8	TSL:1 MANE Select	c.1092T>G	p.Asp364Glu	missense	Exon 8 of 8	ENSP00000306157.3	P16871-1
IL7R	ENST00000505093.1	TSL:2	c.*209T>G		3_prime_UTR	Exon 3 of 3	ENSP00000426069.1	H0YA41
IL7R	ENST00000877114.1		c.783-66T>G		intron	N/A	ENSP00000547173.1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00222

AC:

558

AN:

251008

AF XY:

0.00296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.00109

AC:

1590

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1136

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0175

AC:

1506

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112004

Other (OTH)

AF:

0.00123

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

118

236

354

472

590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000512

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.0162

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000499

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 104 (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0040

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.12

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.42

PhyloP100

-1.7

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.14

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.0080

MutPred

0.12

Loss of catalytic residue at D364 (P = 0.031)

MVP

0.23

MPC

0.014

ClinPred

0.0076

GERP RS

-11

Varity_R

0.045

gMVP

0.087

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over