rs1353251

chr5-35857105-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15

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]

ACMG classification

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/exons	MANE	UniProt
IL7R	NM_002185.5	c.82+46C>T		intron_variant		ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.82+46C>T		intron_variant		1	NM_002185.5	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29068 AN: 151986 Hom.: 3928 Cov.: 32

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

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.: 14 AF XY: 0.242 AC XY: 131678 AN XY: 545176

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.: 32 AF XY: 0.198 AC XY: 14694 AN XY: 74334

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Other links and lift over

dbSNP: rs1353251; hg19: chr5-35857207; COSMIC: COSV57405402;