rs7880291

Positions:

• chrX-71111238-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000206.3(IL2RG):​c.115+187C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 712,445 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 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 0.000030 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000029 (0 hom. 3 hem.)
• Consequence: IL2RG NM_000206.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

Genes affected

IL2RG (HGNC:6010): (interleukin 2 receptor subunit gamma) The protein encoded by this gene is an important signaling component of many interleukin receptors, including those of interleukin -2, -4, -7 and -21, and is thus referred to as the common gamma chain. Mutations in this gene cause X-linked severe combined immunodeficiency (XSCID), as well as X-linked combined immunodeficiency (XCID), a less severe immunodeficiency disorder. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RG	NM_000206.3	c.115+187C>G		intron_variant		ENST00000374202.7
IL2RG	XM_047442089.1	c.115+187C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RG	ENST00000374202.7	c.115+187C>G		intron_variant		1	NM_000206.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000304 AC: 3 AN: 98814 Hom.: 0 Cov.: 22 AF XY: 0.0000393 AC XY: 1 AN XY: 25448

Gnomad AFR AF: 0.0000351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000435

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000293 AC: 18 AN: 613631 Hom.: 0 Cov.: 9 AF XY: 0.0000185 AC XY: 3 AN XY: 162279

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000976

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000248

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000304 AC: 3 AN: 98814 Hom.: 0 Cov.: 22 AF XY: 0.0000393 AC XY: 1 AN XY: 25448

Gnomad4 AFR AF: 0.0000351

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000435

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.41

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: rs7880291; hg19: chrX-70331088; COSMIC: COSV104580002; COSMIC: COSV104580002;