chr5-35873500-A-A

Variant names:

• chr5-35873500-A-A
• ENST00000303115.8:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000303115.8(IL7R):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene IL7R is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL7R ENST00000303115.8 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768
• Publications: 0 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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

Specifications for IL7R are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000303115.8. 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.		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.		intron	N/A	NP_001397663.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.		exon_region	Exon 5 of 8	ENSP00000306157.3	P16871-1
	IL7R	ENST00000877114.1		c.		exon_region	Exon 5 of 7	ENSP00000547173.1
	IL7R	ENST00000506850.5	TSL:2	c.		exon_region	Exon 5 of 6	ENSP00000421207.1	P16871-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-35873602;