Genetic Variant IL7R:c.82+46C>T (chr5-35857105-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002185.5(IL7R):c.82+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,209,236 control chromosomes in the GnomAD database, including 38,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3936 hom., cov: 32)

Exomes 𝑓: 0.24 ( 34974 hom. )

Consequence

IL7R
NM_002185.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.15

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 5-35857105-C-T is Benign according to our data. Variant chr5-35857105-C-T is described in ClinVar as [Benign]. Clinvar id is 1267196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5 link	c.82+46C>T		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+46C>T		intron_variant	Intron 1 of 7	1	NM_002185.5	ENSP00000306157.3		P16871-1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29068

AN:

151986

Hom.:

3928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.274

AC:

67498

AN:

246504

Hom.:

11711

AF XY:

0.273

AC XY:

36478

AN XY:

133732

show subpopulations

Gnomad AFR exome

AF:

0.0408

Gnomad AMR exome

AF:

0.450

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.528

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.238

AC:

251104

AN:

1057132

Hom.:

34974

Cov.:

AF XY:

0.242

AC XY:

131678

AN XY:

545176

show subpopulations

Gnomad4 AFR exome

AF:

0.0396

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.522

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.191

AC:

29082

AN:

152104

Hom.:

3936

Cov.:

AF XY:

0.198

AC XY:

14694

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0446

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.208

Hom.:

1975

Bravo

AF:

0.194

Asia WGS

AF:

0.395

AC:

1375

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1

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 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.7

DANN

Benign

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over