Genetic Variant IL7R:c.*3007A>G (chr5-35879493-A-G) – ACMG Classification: Benign (-20 pts)

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.*3007A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 231,678 control chromosomes in the GnomAD database, including 10,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8138 hom., cov: 33)

Exomes 𝑓: 0.25 ( 2703 hom. )

Consequence

IL7R
NM_002185.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.281

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-35879493-A-G is Benign according to our data. Variant chr5-35879493-A-G is described in ClinVar as Benign. ClinVar VariationId is 907327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 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.*3007A>G	3_prime_UTR	Exon 8 of 8	NP_002176.2
IL7R	NM_001437964.1		c.*3885A>G	3_prime_UTR	Exon 7 of 7	NP_001424893.1
IL7R	NM_001410734.1		c.*3504A>G	3_prime_UTR	Exon 7 of 7	NP_001397663.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.*3007A>G		3_prime_UTR	Exon 8 of 8	ENSP00000306157.3	P16871-1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47155

AN:

151862

Hom.:

8135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.0745

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.247

AC:

19664

AN:

79698

Hom.:

2703

Cov.:

AF XY:

0.246

AC XY:

9029

AN XY:

36652

show subpopulations

African (AFR)

AF:

0.452

AC:

1734

AN:

3834

American (AMR)

AF:

0.209

AC:

515

AN:

2468

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

1395

AN:

5048

East Asian (EAS)

AF:

0.0756

AC:

850

AN:

11250

South Asian (SAS)

AF:

0.198

AC:

138

AN:

698

European-Finnish (FIN)

AF:

0.310

AC:

AN:

Middle Eastern (MID)

AF:

0.313

AC:

151

AN:

482

European-Non Finnish (NFE)

AF:

0.266

AC:

13115

AN:

49216

Other (OTH)

AF:

0.263

AC:

1748

AN:

6644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

704

1408

2113

2817

3521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.310

AC:

47179

AN:

151980

Hom.:

8138

Cov.:

AF XY:

0.308

AC XY:

22871

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.457

AC:

18932

AN:

41440

American (AMR)

AF:

0.234

AC:

3566

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

919

AN:

3468

East Asian (EAS)

AF:

0.0748

AC:

387

AN:

5172

South Asian (SAS)

AF:

0.199

AC:

960

AN:

4814

European-Finnish (FIN)

AF:

0.290

AC:

3062

AN:

10566

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18311

AN:

67940

Other (OTH)

AF:

0.303

AC:

640

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1618

3236

4853

6471

8089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.294

Hom.:

1788

Bravo

AF:

0.312

Asia WGS

AF:

0.163

AC:

568

AN:

3478

ClinVar

ClinVar submissions

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

-0.90

CADD

Benign

5.6

(source)

DANN

Benign

0.64

PhyloP100

0.28

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

Computational scores

Splicing

Publications

Other links and lift over