rs28743771

Variant names:

• chrX-71111272-G-A
• rs28743771
• NM_000206.3:c.115+153C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-71111272-G-A
• chrX-71111272-G-C
• chrX-71111272-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000206.3(IL2RG):​c.115+153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 739,642 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 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 0.000045 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00013 (0 hom. 33 hem.)
• Consequence: IL2RG NM_000206.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, Myriad Women’s Health
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285171 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000454 (5/110168) while in subpopulation EAS AF = 0.000854 (3/3511). AF 95% confidence interval is 0.000233. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 3 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.115+153C>T		intron_variant	Intron 1 of 7	ENST00000374202.7	NP_000197.1
IL2RG	NM_001438870.1	c.115+153C>T		intron_variant	Intron 1 of 6		NP_001425799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.115+153C>T		intron_variant	Intron 1 of 7	1	NM_000206.3	ENSP00000363318.3
ENSG00000285171	ENST00000646505.1	n.115+153C>T		intron_variant	Intron 1 of 11			ENSP00000496673.1

Frequencies

GnomAD3 genomes AF: 0.0000454 AC: 5 AN: 110115 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000852

Gnomad SAS AF: 0.000376

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000191

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 80 AN: 629474 Hom.: 0 Cov.: 10 AF XY: 0.000204 AC XY: 33 AN XY: 161730

African (AFR) AF: 0.00 AC: 0 AN: 15958

American (AMR) AF: 0.00 AC: 0 AN: 19941

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12727

East Asian (EAS) AF: 0.00115 AC: 29 AN: 25231

South Asian (SAS) AF: 0.000741 AC: 26 AN: 35099

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1910

European-Non Finnish (NFE) AF: 0.0000349 AC: 16 AN: 458249

Other (OTH) AF: 0.000302 AC: 9 AN: 29835

GnomAD4 genome AF: 0.0000454 AC: 5 AN: 110168 Hom.: 0 Cov.: 23 AF XY: 0.0000918 AC XY: 3 AN XY: 32692

African (AFR) AF: 0.00 AC: 0 AN: 30382

American (AMR) AF: 0.00 AC: 0 AN: 10399

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2600

East Asian (EAS) AF: 0.000854 AC: 3 AN: 3511

South Asian (SAS) AF: 0.000378 AC: 1 AN: 2649

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 211

European-Non Finnish (NFE) AF: 0.0000191 AC: 1 AN: 52385

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.029
DANN	Benign	0.40
PhyloP100		-1.7
PromoterAI		-0.047	Neutral
Mutation Taster		=100/0	polymorphism

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: rs28743771; hg19: chrX-70331122;