Variant 5-35877739-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002185.5(IL7R):c.*1253G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 233,064 control chromosomes in the GnomAD database, including 9,403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6799 hom., cov: 32)

Exomes 𝑓: 0.24 ( 2604 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

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:

IL7R (HGNC:):

IL7R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-35877739-G-A is Benign according to our data. Variant chr5-35877739-G-A is described in ClinVar as [Benign]. Clinvar id is 353288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
IL7R	NM_002185.5 linkuse as main transcript	c.*1253G>A	3_prime_UTR_variant	8/8	ENST00000303115.8	NP_002176.2	P16871-1
IL7R	NM_001410734.1 linkuse as main transcript	c.*1750G>A	3_prime_UTR_variant	7/7		NP_001397663.1
IL7R	NR_120485.3 linkuse as main transcript	n.2457G>A	non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8 linkuse as main transcript	c.*1253G>A		3_prime_UTR_variant	8/8	1	NM_002185.5	ENSP00000306157.3		P16871-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43893

AN:

151982

Hom.:

6798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.243

AC:

19653

AN:

80964

Hom.:

2604

Cov.:

AF XY:

0.243

AC XY:

9049

AN XY:

37210

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.0760

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.289

AC:

43897

AN:

152100

Hom.:

6799

Cov.:

AF XY:

0.286

AC XY:

21266

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.265

Gnomad4 EAS

AF:

0.0727

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.190

Hom.:

494

Bravo

AF:

0.298

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Immunodeficiency 104

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.59

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