rs3134883

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000417.3(IL2RA):​c.64+3326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,084 control chromosomes in the GnomAD database, including 5,027 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 0.23 ( 5027 hom., cov: 32)

Consequence

IL2RA
NM_000417.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.244
Variant links:
Genes affected
IL2RA (HGNC:6008): (interleukin 2 receptor subunit alpha) The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL2 receptor. Homodimeric alpha chains (IL2RA) result in low-affinity receptor, while homodimeric beta (IL2RB) chains produce a medium-affinity receptor. Normally an integral-membrane protein, soluble IL2RA has been isolated and determined to result from extracellular proteolyisis. Alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is presently unknown. Mutations in this gene are associated with interleukin 2 receptor alpha deficiency. Patients with severe Coronavirus Disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have significantly elevated levels of IL2R in their plasma. Similarly, serum IL-2R levels are found to be elevated in patients with different types of carcinomas. Certain IL2RA and IL2RB gene polymorphisms have been associated with lung cancer risk. [provided by RefSeq, Jul 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL2RANM_000417.3 linkuse as main transcriptc.64+3326C>T intron_variant ENST00000379959.8
IL2RANM_001308242.2 linkuse as main transcriptc.64+3326C>T intron_variant
IL2RANM_001308243.2 linkuse as main transcriptc.64+3326C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL2RAENST00000379959.8 linkuse as main transcriptc.64+3326C>T intron_variant 1 NM_000417.3 P1

Frequencies

GnomAD3 genomes
AF:
0.230
AC:
34935
AN:
151964
Hom.:
5020
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0696
Gnomad AMI
AF:
0.387
Gnomad AMR
AF:
0.204
Gnomad ASJ
AF:
0.174
Gnomad EAS
AF:
0.259
Gnomad SAS
AF:
0.315
Gnomad FIN
AF:
0.359
Gnomad MID
AF:
0.171
Gnomad NFE
AF:
0.306
Gnomad OTH
AF:
0.228
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.230
AC:
34947
AN:
152084
Hom.:
5027
Cov.:
32
AF XY:
0.233
AC XY:
17306
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0694
Gnomad4 AMR
AF:
0.204
Gnomad4 ASJ
AF:
0.174
Gnomad4 EAS
AF:
0.259
Gnomad4 SAS
AF:
0.316
Gnomad4 FIN
AF:
0.359
Gnomad4 NFE
AF:
0.306
Gnomad4 OTH
AF:
0.231
Alfa
AF:
0.291
Hom.:
3200
Bravo
AF:
0.207
Asia WGS
AF:
0.277
AC:
966
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
3.7
DANN
Benign
0.55

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.

Other links and lift over

dbSNP: rs3134883; hg19: chr10-6100725; API