rs4073970

Positions:

• chrX-71109942-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000285171 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.594+214T>C		intron_variant		ENST00000374202.7	NP_000197.1
IL2RG	XM_047442089.1	c.594+214T>C		intron_variant			XP_047298045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.594+214T>C		intron_variant		1	NM_000206.3	ENSP00000363318.3
ENSG00000285171	ENST00000646505.1	n.594+214T>C		intron_variant				ENSP00000496673.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 12066 AN: 102612 Hom.: 888 Cov.: 18 AF XY: 0.0555 AC XY: 1525 AN XY: 27464

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

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0800

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0481 Hom.: 176

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.90

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: rs4073970; hg19: chrX-70329792;