dbSNP rs11567685: IL7R:c.-216T>C (chr5-35856473-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000515665.1(IL7R):c.-216T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 157,252 control chromosomes in the GnomAD database, including 5,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5364 hom., cov: 33)

Exomes 𝑓: 0.19 ( 116 hom. )

Consequence

IL7R
ENST00000515665.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.540

Publications

6 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL7R	ENST00000515665.1 link	c.-216T>C	5_prime_UTR_variant	Exon 1 of 3	4	ENSP00000425538.1	D6RCR9
IL7R	ENST00000508941.5 link	c.-2+304T>C	intron_variant	Intron 2 of 3	4	ENSP00000426426.1	D6RG28
IL7R	ENST00000511031.1 link	n.216+3535T>C	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39361

AN:

152014

Hom.:

5361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.0447

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.187

AC:

959

AN:

5120

Hom.:

116

Cov.:

AF XY:

0.185

AC XY:

497

AN XY:

2686

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.157

AC:

153

AN:

974

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.0288

AC:

AN:

208

South Asian (SAS)

AF:

0.140

AC:

AN:

508

European-Finnish (FIN)

AF:

0.139

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.213

AC:

674

AN:

3164

Other (OTH)

AF:

0.202

AC:

AN:

188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.259

AC:

39361

AN:

152132

Hom.:

5364

Cov.:

AF XY:

0.257

AC XY:

19106

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.278

AC:

11542

AN:

41486

American (AMR)

AF:

0.218

AC:

3335

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3470

East Asian (EAS)

AF:

0.0448

AC:

232

AN:

5180

South Asian (SAS)

AF:

0.199

AC:

958

AN:

4822

European-Finnish (FIN)

AF:

0.289

AC:

3054

AN:

10562

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18370

AN:

68008

Other (OTH)

AF:

0.263

AC:

555

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1499

2997

4496

5994

7493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.265

Hom.:

11816

Bravo

AF:

0.253

Asia WGS

AF:

0.141

AC:

491

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.6

(source)

DANN

Benign

0.40

PhyloP100

0.54

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over