NM_002185.5:c.537+369C>T

Variant names:

• chr5-35871582-C-T
• rs11567751
• NM_002185.5:c.537+369C>T

Variant summary

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

The NM_002185.5(IL7R):​c.537+369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,096 control chromosomes in the GnomAD database, including 5,322 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 0.26 (5322 hom., cov: 33)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 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.537+369C>T		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.537+369C>T		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.537+369C>T		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.537+369C>T		intron	N/A	ENSP00000306157.3
	IL7R	ENST00000877114.1		c.537+369C>T		intron	N/A	ENSP00000547173.1
	IL7R	ENST00000506850.5	TSL:2	c.537+369C>T		intron	N/A	ENSP00000421207.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39336 AN: 151978 Hom.: 5321 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.259 AC: 39334 AN: 152096 Hom.: 5322 Cov.: 33 AF XY: 0.257 AC XY: 19091 AN XY: 74332

African (AFR) AF: 0.277 AC: 11499 AN: 41478

American (AMR) AF: 0.216 AC: 3303 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3472

East Asian (EAS) AF: 0.0731 AC: 379 AN: 5186

South Asian (SAS) AF: 0.198 AC: 953 AN: 4820

European-Finnish (FIN) AF: 0.289 AC: 3048 AN: 10540

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18279 AN: 68004

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.191 Hom.: 531

Bravo AF: 0.253

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.87
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: rs11567751; hg19: chr5-35871684;