rs7910961

chr10-6035833-T-C

Variant summary

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

The NM_000417.3(IL2RA):c.65-9808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,212 control chromosomes in the GnomAD database, including 39,546 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 0.71 (39534 hom., cov: 32)
  • Exomes 𝑓: 0.64 (12 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

LOC107984201 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RA	NM_000417.3	c.65-9808A>G		intron_variant		ENST00000379959.8
LOC107984201	XR_001747349.2	n.424T>C		non_coding_transcript_exon_variant	1/2
IL2RA	NM_001308242.2	c.65-9808A>G		intron_variant
IL2RA	NM_001308243.2	c.65-9808A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RA	ENST00000379959.8	c.65-9808A>G		intron_variant		1	NM_000417.3	P1
	ENST00000440436.1	n.92-107T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108593 AN: 152036 Hom.: 39487 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.643 AC: 36 AN: 56 Hom.: 12 AF XY: 0.682 AC XY: 30 AN XY: 44

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.714 AC: 108697 AN: 152156 Hom.: 39534 Cov.: 32 AF XY: 0.715 AC XY: 53197 AN XY: 74382

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.682

Alfa AF: 0.666 Hom.: 69322

Bravo AF: 0.708

Asia WGS AF: 0.854 AC: 2971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.52
Dann	Benign	0.19

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: rs7910961; hg19: chr10-6077796;