rs1494558

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: NM_002185.5(IL7R):c.197T>C is a missense variant predicted to cause substitution of Isoleucine by Threonine at amino acid 66 (p.Ile66Thr). The filtering allele frequency (the lower threshold of the 95% CI of 56371/74906 alleles) of the c.197T>C variant in IL7R is 0.7458 for African/African American chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1, and therefore meets this criterion (BA1). Additionally, 353136 homozygotes have been described.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. Criteria applied: BA1 (VCEP specifications version 1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA124390/MONDO:0012163/119

Frequency

Genomes: 𝑓 0.67 ( 34940 hom., cov: 32)

Exomes 𝑓: 0.66 ( 318196 hom. )

Consequence

IL7R
NM_002185.5 missense

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:13O:2

Conservation

PhyloP100: 0.311

Publications

115 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: 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

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.197T>C	p.Ile66Thr	missense	Exon 2 of 8	NP_002176.2
IL7R	NM_001437964.1		c.197T>C	p.Ile66Thr	missense	Exon 2 of 7	NP_001424893.1
IL7R	NM_001410734.1		c.197T>C	p.Ile66Thr	missense	Exon 2 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.197T>C	p.Ile66Thr	missense	Exon 2 of 8	ENSP00000306157.3	P16871-1
IL7R	ENST00000877114.1		c.197T>C	p.Ile66Thr	missense	Exon 2 of 7	ENSP00000547173.1
IL7R	ENST00000506850.5	TSL:2	c.197T>C	p.Ile66Thr	missense	Exon 2 of 6	ENSP00000421207.1	P16871-3

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

102247

AN:

151946

Hom.:

34942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.647

GnomAD2 exomes

AF:

0.618

AC:

155256

AN:

251092

AF XY:

0.619

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.648

GnomAD4 exome

AF:

0.656

AC:

958630

AN:

1460288

Hom.:

318196

Cov.:

AF XY:

0.652

AC XY:

473998

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.754

AC:

25185

AN:

33422

American (AMR)

AF:

0.506

AC:

22623

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

16437

AN:

26100

East Asian (EAS)

AF:

0.423

AC:

16782

AN:

39680

South Asian (SAS)

AF:

0.516

AC:

44525

AN:

86220

European-Finnish (FIN)

AF:

0.732

AC:

39093

AN:

53418

Middle Eastern (MID)

AF:

0.602

AC:

3472

AN:

5764

European-Non Finnish (NFE)

AF:

0.677

AC:

751631

AN:

1110650

Other (OTH)

AF:

0.644

AC:

38882

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16801

33602

50402

67203

84004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19274

38548

57822

77096

96370

<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:

0.673

AC:

102273

AN:

152064

Hom.:

34940

Cov.:

AF XY:

0.669

AC XY:

49718

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.752

AC:

31186

AN:

41484

American (AMR)

AF:

0.562

AC:

8583

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2211

AN:

3466

East Asian (EAS)

AF:

0.419

AC:

2165

AN:

5164

South Asian (SAS)

AF:

0.509

AC:

2449

AN:

4816

European-Finnish (FIN)

AF:

0.736

AC:

7777

AN:

10568

Middle Eastern (MID)

AF:

0.630

AC:

184

AN:

292

European-Non Finnish (NFE)

AF:

0.671

AC:

45636

AN:

67990

Other (OTH)

AF:

0.642

AC:

1355

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1661

3323

4984

6646

8307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.666

Hom.:

120713

Bravo

AF:

0.666

TwinsUK

AF:

0.679

AC:

2519

ALSPAC

AF:

0.682

AC:

2628

ESP6500AA

AF:

0.754

AC:

3323

ESP6500EA

AF:

0.674

AC:

5793

ExAC

AF:

0.627

AC:

76188

Asia WGS

AF:

0.524

AC:

1821

AN:

3478

EpiCase

AF:

0.666

EpiControl

AF:

0.674

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 104 (6)

not specified (6)

not provided (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.55

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.95

PhyloP100

0.31

PrimateAI

Benign

0.34

PROVEAN

Benign

2.1

REVEL

Benign

0.091

Sift

Benign

0.88

Sift4G

Benign

0.73

Vest4

0.023

MPC

0.015

ClinPred

0.0014

GERP RS

2.2

Varity_R

0.074

gMVP

0.18

Mutation Taster

=100/0

polymorphism (auto)

(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