rs9292618

Variant names:

• chr5-35878410-G-A
• rs9292618
• NM_002185.5:c.*1924G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002185.5(IL7R):​c.*1924G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 232,966 control chromosomes in the GnomAD database, including 2,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1318 hom., cov: 33)
  • Exomes 𝑓: 0.13 (748 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61
• Publications: 6 publications found

Genes affected

IL7R (HGNC:6024): (interleukin 7 receptor) The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found. [provided by RefSeq, Dec 2015]

IL7R Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-35878410-G-A is Benign according to our data. Variant chr5-35878410-G-A is described in ClinVar as Benign. ClinVar VariationId is 353301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002185.5. 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
	IL7R	NM_002185.5	MANE Select	c.*1924G>A		3_prime_UTR	Exon 8 of 8	NP_002176.2
	IL7R	NM_001437964.1		c.*2802G>A		3_prime_UTR	Exon 7 of 7	NP_001424893.1
	IL7R	NM_001410734.1		c.*2421G>A		3_prime_UTR	Exon 7 of 7	NP_001397663.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.*1924G>A		3_prime_UTR	Exon 8 of 8	ENSP00000306157.3	P16871-1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19948 AN: 152060 Hom.: 1318 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.134 AC: 10808 AN: 80788 Hom.: 748 Cov.: 0 AF XY: 0.134 AC XY: 4968 AN XY: 37124

African (AFR) AF: 0.133 AC: 516 AN: 3892

American (AMR) AF: 0.157 AC: 392 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 593 AN: 5110

East Asian (EAS) AF: 0.112 AC: 1274 AN: 11366

South Asian (SAS) AF: 0.0500 AC: 35 AN: 700

European-Finnish (FIN) AF: 0.138 AC: 8 AN: 58

Middle Eastern (MID) AF: 0.112 AC: 55 AN: 490

European-Non Finnish (NFE) AF: 0.139 AC: 6963 AN: 49916

Other (OTH) AF: 0.144 AC: 972 AN: 6758

GnomAD4 genome AF: 0.131 AC: 19940 AN: 152178 Hom.: 1318 Cov.: 33 AF XY: 0.128 AC XY: 9513 AN XY: 74394

African (AFR) AF: 0.131 AC: 5444 AN: 41506

American (AMR) AF: 0.143 AC: 2188 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.144 AC: 746 AN: 5182

South Asian (SAS) AF: 0.0628 AC: 303 AN: 4826

European-Finnish (FIN) AF: 0.100 AC: 1064 AN: 10600

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9265 AN: 67996

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.134 Hom.: 219

Bravo AF: 0.139

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 104 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.075
DANN	Benign	0.41
PhyloP100		-1.6
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: rs9292618; hg19: chr5-35878512;