ENST00000508941.5:c.-139-724T>C

Variant names:

• chr5-35855308-T-C
• rs4869492
• ENST00000508941.5:c.-139-724T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000508941.5(IL7R):​c.-139-724T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,204 control chromosomes in the GnomAD database, including 1,247 homozygotes. 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 0.13 (1247 hom., cov: 32)
• Consequence: IL7R ENST00000508941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508941.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000508941.5	TSL:4	c.-139-724T>C		intron	N/A	ENSP00000426426.1
	IL7R	ENST00000511031.1	TSL:3	n.216+2370T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19491 AN: 152086 Hom.: 1247 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.128 AC: 19481 AN: 152204 Hom.: 1247 Cov.: 32 AF XY: 0.125 AC XY: 9320 AN XY: 74412

African (AFR) AF: 0.130 AC: 5399 AN: 41518

American (AMR) AF: 0.144 AC: 2206 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3470

East Asian (EAS) AF: 0.144 AC: 745 AN: 5176

South Asian (SAS) AF: 0.0627 AC: 302 AN: 4814

European-Finnish (FIN) AF: 0.0983 AC: 1042 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8875 AN: 68006

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.135 Hom.: 1761

Bravo AF: 0.136

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.79
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4869492; hg19: chr5-35855410;