X-71110746-T-C

Variant names:

• chrX-71110746-T-C
• rs11574625
• NM_000206.3:c.270-58A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000206.3(IL2RG):​c.270-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,107,988 control chromosomes in the GnomAD database, including 18,066 homozygotes. There are 63,864 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (4157 hom., 8494 hem., cov: 22)
  • Exomes 𝑓: 0.17 (13909 hom. 55370 hem.)
• Consequence: IL2RG NM_000206.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.511
• Publications: 6 publications found

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]

IL2RG Gene-Disease associations (from GenCC):

• T-B+ severe combined immunodeficiency due to gamma chain deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, Myriad Women’s Health
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285171 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-71110746-T-C is Benign according to our data. Variant chrX-71110746-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000206.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RG	NM_000206.3	MANE Select	c.270-58A>G		intron	N/A	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.270-58A>G		intron	N/A	NP_001425799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RG	ENST00000374202.7	TSL:1 MANE Select	c.270-58A>G		intron	N/A	ENSP00000363318.3	P31785-1
	ENSG00000285171	ENST00000646505.1		n.270-58A>G		intron	N/A	ENSP00000496673.1	A0A2R8YE73
	IL2RG	ENST00000482750.6	TSL:5	c.270-58A>G		intron	N/A	ENSP00000421262.2	H0Y8J6

Frequencies

GnomAD3 genomes AF: 0.270 AC: 29849 AN: 110356 Hom.: 4156 Cov.: 22

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.0235

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.175 AC: 174351 AN: 997575 Hom.: 13909 Cov.: 20 AF XY: 0.191 AC XY: 55370 AN XY: 290345

African (AFR) AF: 0.528 AC: 12975 AN: 24576

American (AMR) AF: 0.471 AC: 16123 AN: 34212

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 2528 AN: 18712

East Asian (EAS) AF: 0.318 AC: 9415 AN: 29622

South Asian (SAS) AF: 0.354 AC: 18214 AN: 51429

European-Finnish (FIN) AF: 0.122 AC: 4910 AN: 40115

Middle Eastern (MID) AF: 0.154 AC: 591 AN: 3828

European-Non Finnish (NFE) AF: 0.134 AC: 101057 AN: 752267

Other (OTH) AF: 0.199 AC: 8538 AN: 42814

GnomAD4 genome AF: 0.271 AC: 29888 AN: 110413 Hom.: 4157 Cov.: 22 AF XY: 0.260 AC XY: 8494 AN XY: 32665

African (AFR) AF: 0.511 AC: 15403 AN: 30140

American (AMR) AF: 0.378 AC: 3904 AN: 10319

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 352 AN: 2629

East Asian (EAS) AF: 0.304 AC: 1060 AN: 3491

South Asian (SAS) AF: 0.367 AC: 966 AN: 2635

European-Finnish (FIN) AF: 0.113 AC: 678 AN: 5983

Middle Eastern (MID) AF: 0.144 AC: 31 AN: 215

European-Non Finnish (NFE) AF: 0.134 AC: 7083 AN: 52818

Other (OTH) AF: 0.263 AC: 395 AN: 1502

Alfa AF: 0.199 Hom.: 15593

Bravo AF: 0.305

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11574625; hg19: chrX-70330596; COSMIC: COSV52147135; COSMIC: COSV52147135;