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.*1253G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 233,124 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 16 hom. )

Consequence

IL7R
NM_002185.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.130

Publications

7 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=-0.84).

BP6

Variant 5-35877739-G-T is Benign according to our data. Variant chr5-35877739-G-T is described in ClinVar as Benign. ClinVar VariationId is 353289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

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	Effect	Exon Rank	Protein
IL7R	NM_002185.5	MANE Select	c.*1253G>T	3_prime_UTR	Exon 8 of 8	NP_002176.2
IL7R	NR_120485.3		n.2457G>T	non_coding_transcript_exon	Exon 6 of 6
IL7R	NM_001437964.1		c.*2131G>T	3_prime_UTR	Exon 7 of 7	NP_001424893.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.*1253G>T		3_prime_UTR	Exon 8 of 8	ENSP00000306157.3

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3263

AN:

152034

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0229

GnomAD4 exome

AF:

0.00524

AC:

424

AN:

80972

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

170

AN XY:

37212

show subpopulations

African (AFR)

AF:

0.0813

AC:

317

AN:

3900

American (AMR)

AF:

0.00800

AC:

AN:

2500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5124

East Asian (EAS)

AF:

0.00

AC:

AN:

11410

South Asian (SAS)

AF:

0.00

AC:

AN:

702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00407

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.000240

AC:

AN:

50014

Other (OTH)

AF:

0.0108

AC:

AN:

6770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0216

AC:

3283

AN:

152152

Hom.:

115

Cov.:

AF XY:

0.0213

AC XY:

1588

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0747

AC:

3098

AN:

41488

American (AMR)

AF:

0.00746

AC:

114

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68016

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

151

302

453

604

755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00

Hom.:

494

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 104 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.90

(source)

DANN

Benign

0.65

PhyloP100

-0.13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over