NM_002185.5:c.82+689A>C

Variant names:

• chr5-35857748-A-C
• rs10213865
• NM_002185.5:c.82+689A>C

Variant summary

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

The NM_002185.5(IL7R):​c.82+689A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,006 control chromosomes in the GnomAD database, including 4,793 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 0.25 (4793 hom., cov: 31)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 24 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	NM_002185.5	MANE Select	c.82+689A>C		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.82+689A>C		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.82+689A>C		intron	N/A	NP_001397663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.82+689A>C		intron	N/A	ENSP00000306157.3
	IL7R	ENST00000506850.5	TSL:2	c.82+689A>C		intron	N/A	ENSP00000421207.1
	IL7R	ENST00000511982.1	TSL:2	c.82+689A>C		intron	N/A	ENSP00000425309.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37358 AN: 151888 Hom.: 4792 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.246 AC: 37384 AN: 152006 Hom.: 4793 Cov.: 31 AF XY: 0.248 AC XY: 18433 AN XY: 74292

African (AFR) AF: 0.212 AC: 8805 AN: 41472

American (AMR) AF: 0.190 AC: 2897 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1192 AN: 5180

South Asian (SAS) AF: 0.247 AC: 1189 AN: 4812

European-Finnish (FIN) AF: 0.344 AC: 3633 AN: 10554

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18038 AN: 67940

Other (OTH) AF: 0.216 AC: 455 AN: 2106

Alfa AF: 0.159 Hom.: 391

Bravo AF: 0.233

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.37
PhyloP100		-0.027
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: rs10213865; hg19: chr5-35857850;