Genetic Variant IL7R:c.706+122T>G (chr5-35873770-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002185.5(IL7R):c.706+122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 876,188 control chromosomes in the GnomAD database, including 29,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 5945 hom., cov: 32)

Exomes 𝑓: 0.25 ( 23914 hom. )

Consequence

IL7R
NM_002185.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.209

Publications

10 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-35873770-T-G is Benign according to our data. Variant chr5-35873770-T-G is described in ClinVar as Benign. ClinVar VariationId is 1183897.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5 link	c.706+122T>G		intron_variant	Intron 5 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.706+122T>G		intron_variant	Intron 5 of 7	1	NM_002185.5	ENSP00000306157.3		P16871-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41347

AN:

151978

Hom.:

5944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.0724

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.250

AC:

180812

AN:

724092

Hom.:

23914

AF XY:

0.249

AC XY:

96432

AN XY:

386632

show subpopulations

African (AFR)

AF:

0.320

AC:

6059

AN:

18928

American (AMR)

AF:

0.159

AC:

6548

AN:

41108

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

5791

AN:

21314

East Asian (EAS)

AF:

0.0710

AC:

2514

AN:

35390

South Asian (SAS)

AF:

0.207

AC:

14322

AN:

69210

European-Finnish (FIN)

AF:

0.294

AC:

14961

AN:

50896

Middle Eastern (MID)

AF:

0.294

AC:

820

AN:

2788

European-Non Finnish (NFE)

AF:

0.269

AC:

120824

AN:

448462

Other (OTH)

AF:

0.249

AC:

8973

AN:

35996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7481

14963

22444

29926

37407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1778

3556

5334

7112

8890

<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:

0.272

AC:

41349

AN:

152096

Hom.:

5945

Cov.:

AF XY:

0.270

AC XY:

20054

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.324

AC:

13437

AN:

41486

American (AMR)

AF:

0.220

AC:

3356

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

919

AN:

3470

East Asian (EAS)

AF:

0.0728

AC:

377

AN:

5182

South Asian (SAS)

AF:

0.199

AC:

958

AN:

4822

European-Finnish (FIN)

AF:

0.289

AC:

3054

AN:

10568

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18278

AN:

67970

Other (OTH)

AF:

0.268

AC:

567

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1538

3075

4613

6150

7688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.194

Hom.:

525

Bravo

AF:

0.267

Asia WGS

AF:

0.151

AC:

524

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 03, 2015

GeneDx

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

-0.83

CADD

Benign

3.7

(source)

DANN

Benign

0.45

PhyloP100

0.21

PromoterAI

0.014

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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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