rs11567685

chr5-35856473-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540

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 -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000515665.1	c.-216T>C		5_prime_UTR_variant	1/3	4
IL7R	ENST00000508941.5	c.-2+304T>C		intron_variant		4
IL7R	ENST00000511031.1	n.216+3535T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39361 AN: 152014 Hom.: 5361 Cov.: 33

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.: 0 AF XY: 0.185 AC XY: 497 AN XY: 2686

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.0288

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.259 AC: 39361 AN: 152132 Hom.: 5364 Cov.: 33 AF XY: 0.257 AC XY: 19106 AN XY: 74354

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.263

Alfa AF: 0.267 Hom.: 8703

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
Dann	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11567685; hg19: chr5-35856575;