rs4073970

Variant names:

• chrX-71109942-A-G
• rs4073970
• NM_000206.3:c.594+214T>C

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.594+214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (891 hom., 1532 hem., cov: 18)
• Consequence: IL2RG NM_000206.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-71109942-A-G is Benign according to our data. Variant chrX-71109942-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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.594+214T>C		intron	N/A	NP_000197.1
	IL2RG	NM_001438870.1		c.594+214T>C		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.594+214T>C		intron	N/A	ENSP00000363318.3
	ENSG00000285171	ENST00000646505.1		n.594+214T>C		intron	N/A	ENSP00000496673.1
	IL2RG	ENST00000482750.6	TSL:5	c.594+214T>C		intron	N/A	ENSP00000421262.2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 12066 AN: 102612 Hom.: 888 Cov.: 18

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.100

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.118 AC: 12074 AN: 102639 Hom.: 891 Cov.: 18 AF XY: 0.0557 AC XY: 1532 AN XY: 27503

African (AFR) AF: 0.193 AC: 5191 AN: 26844

American (AMR) AF: 0.0800 AC: 765 AN: 9558

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 162 AN: 2588

East Asian (EAS) AF: 0.0993 AC: 336 AN: 3383

South Asian (SAS) AF: 0.140 AC: 312 AN: 2225

European-Finnish (FIN) AF: 0.0544 AC: 260 AN: 4776

Middle Eastern (MID) AF: 0.105 AC: 22 AN: 209

European-Non Finnish (NFE) AF: 0.0939 AC: 4790 AN: 51001

Other (OTH) AF: 0.115 AC: 161 AN: 1403

Alfa AF: 0.0481 Hom.: 176

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.90
PhyloP100		0.21
PromoterAI		-0.0029	Neutral
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: rs4073970; hg19: chrX-70329792;