rs987106

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002185.5(IL7R):c.801-21A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,562,986 control chromosomes in the GnomAD database, including 215,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21185 hom., cov: 32)

Exomes 𝑓: 0.52 ( 194037 hom. )

Consequence

IL7R
NM_002185.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.139

Publications

36 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-35875491-A-T is Benign according to our data. Variant chr5-35875491-A-T is described in ClinVar as Benign. ClinVar VariationId is 1165796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5 link	c.801-21A>T		intron_variant	Intron 6 of 7	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8 link	c.801-21A>T		intron_variant	Intron 6 of 7	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79445

AN:

151860

Hom.:

21184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.650

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.635

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.535

Gnomad OTH

AF:

0.489

GnomAD2 exomes

AF:

0.488

AC:

121833

AN:

249882

AF XY:

0.494

show subpopulations

Gnomad AFR exome

AF:

0.562

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.632

Gnomad NFE exome

AF:

0.537

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.520

AC:

734085

AN:

1411008

Hom.:

194037

Cov.:

AF XY:

0.519

AC XY:

366303

AN XY:

705146

show subpopulations

African (AFR)

AF:

0.560

AC:

18130

AN:

32396

American (AMR)

AF:

0.349

AC:

15533

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

13169

AN:

25834

East Asian (EAS)

AF:

0.290

AC:

11438

AN:

39420

South Asian (SAS)

AF:

0.456

AC:

38851

AN:

85154

European-Finnish (FIN)

AF:

0.631

AC:

33681

AN:

53336

Middle Eastern (MID)

AF:

0.457

AC:

2599

AN:

5686

European-Non Finnish (NFE)

AF:

0.536

AC:

570995

AN:

1065954

Other (OTH)

AF:

0.506

AC:

29689

AN:

58684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16857

33714

50572

67429

84286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15864

31728

47592

63456

79320

<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:

0.523

AC:

79473

AN:

151978

Hom.:

21185

Cov.:

AF XY:

0.523

AC XY:

38851

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.556

AC:

23017

AN:

41420

American (AMR)

AF:

0.412

AC:

6286

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1759

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1415

AN:

5152

South Asian (SAS)

AF:

0.446

AC:

2148

AN:

4812

European-Finnish (FIN)

AF:

0.635

AC:

6712

AN:

10570

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.535

AC:

36369

AN:

67966

Other (OTH)

AF:

0.487

AC:

1027

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1950

3900

5849

7799

9749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.530

Hom.:

3949

Bravo

AF:

0.506

Asia WGS

AF:

0.412

AC:

1432

AN:

3478

EpiCase

AF:

0.526

EpiControl

AF:

0.537

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19523791, 17660816, 15674389) -

Immunodeficiency 104

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.081

(source)

DANN

Benign

0.40

PhyloP100

-0.14

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over