5-35857075-G-C

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.82+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,504,278 control chromosomes in the GnomAD database, including 335,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39202 hom., cov: 31)

Exomes 𝑓: 0.66 ( 295827 hom. )

Consequence

IL7R
NM_002185.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.54

Publications

21 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=-0.88).

BP6

Variant 5-35857075-G-C is Benign according to our data. Variant chr5-35857075-G-C is described in ClinVar as [Benign]. Clinvar id is 258579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5 link	c.82+16G>C		intron_variant	Intron 1 of 7	ENST00000303115.8	NP_002176.2	P16871-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8 link	c.82+16G>C		intron_variant	Intron 1 of 7	1	NM_002185.5	ENSP00000306157.3		P16871-1

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

107499

AN:

151956

Hom.:

39184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.672

Gnomad OTH

AF:

0.678

GnomAD2 exomes

AF:

0.627

AC:

155530

AN:

248058

AF XY:

0.625

show subpopulations

Gnomad AFR exome

AF:

0.879

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.657

AC:

888434

AN:

1352202

Hom.:

295827

Cov.:

AF XY:

0.653

AC XY:

443204

AN XY:

678930

show subpopulations

African (AFR)

AF:

0.880

AC:

27474

AN:

31212

American (AMR)

AF:

0.512

AC:

22835

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

16033

AN:

25488

East Asian (EAS)

AF:

0.421

AC:

16496

AN:

39168

South Asian (SAS)

AF:

0.516

AC:

43460

AN:

84208

European-Finnish (FIN)

AF:

0.732

AC:

38146

AN:

52136

Middle Eastern (MID)

AF:

0.610

AC:

3417

AN:

5598

European-Non Finnish (NFE)

AF:

0.675

AC:

683446

AN:

1012940

Other (OTH)

AF:

0.653

AC:

37127

AN:

56854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

14417

28835

43252

57670

72087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.707

AC:

107565

AN:

152076

Hom.:

39202

Cov.:

AF XY:

0.702

AC XY:

52165

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.872

AC:

36196

AN:

41498

American (AMR)

AF:

0.574

AC:

8767

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2212

AN:

3468

East Asian (EAS)

AF:

0.417

AC:

2155

AN:

5172

South Asian (SAS)

AF:

0.511

AC:

2461

AN:

4820

European-Finnish (FIN)

AF:

0.735

AC:

7749

AN:

10536

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.672

AC:

45682

AN:

67980

Other (OTH)

AF:

0.676

AC:

1429

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.625

Hom.:

3663

Bravo

AF:

0.706

Asia WGS

AF:

0.553

AC:

1924

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Immunodeficiency 104

Benign:2

Feb 03, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.8

(source)

DANN

Benign

0.60

PhyloP100

-1.5

PromoterAI

0.039

Neutral

(source)

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

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5-35857075-G-C

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