Variant rs12722574 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000417.3(IL2RA):c.257-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 678,636 control chromosomes in the GnomAD database, including 17,997 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 ( 6096 hom., cov: 33)

Exomes 𝑓: 0.20 ( 11901 hom. )

Consequence

IL2RA
NM_000417.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492

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]

IL2RA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
IL2RA	NM_000417.3 linkuse as main transcript	c.257-145C>T	intron_variant	ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2 linkuse as main transcript	c.257-145C>T	intron_variant		NP_001295171.1
IL2RA	NM_001308243.2 linkuse as main transcript	c.257-145C>T	intron_variant		NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 linkuse as main transcript	c.257-145C>T		intron_variant		1	NM_000417.3	ENSP00000369293	P1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39429

AN:

152006

Hom.:

6087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.203

AC:

107005

AN:

526512

Hom.:

11901

AF XY:

0.204

AC XY:

57150

AN XY:

279866

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.259

AC:

39468

AN:

152124

Hom.:

6096

Cov.:

AF XY:

0.253

AC XY:

18808

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.435

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.241

Hom.:

1077

Bravo

AF:

0.268

Asia WGS

AF:

0.200

AC:

698

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

DANN

Benign

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over