NM_002185.5:c.380-1340G>A

Variant names:

• chr5-35869716-G-A
• rs10941267
• NM_002185.5:c.380-1340G>A

Variant summary

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

The NM_002185.5(IL7R):​c.380-1340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,044 control chromosomes in the GnomAD database, including 37,128 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 0.69 (37128 hom., cov: 31)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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.380-1340G>A		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.380-1340G>A		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.380-1340G>A		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.380-1340G>A		intron	N/A	ENSP00000306157.3
	IL7R	ENST00000506850.5	TSL:2	c.380-1340G>A		intron	N/A	ENSP00000421207.1
	IL7R	ENST00000514217.5	TSL:2	n.380-1340G>A		intron	N/A	ENSP00000427688.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105263 AN: 151924 Hom.: 37109 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.693 AC: 105326 AN: 152044 Hom.: 37128 Cov.: 31 AF XY: 0.689 AC XY: 51201 AN XY: 74316

African (AFR) AF: 0.799 AC: 33157 AN: 41484

American (AMR) AF: 0.572 AC: 8734 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2263 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2444 AN: 5146

South Asian (SAS) AF: 0.542 AC: 2613 AN: 4818

European-Finnish (FIN) AF: 0.742 AC: 7849 AN: 10574

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45928 AN: 67960

Other (OTH) AF: 0.674 AC: 1422 AN: 2110

Alfa AF: 0.655 Hom.: 6924

Bravo AF: 0.687

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.60
PhyloP100		-0.19
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: rs10941267; hg19: chr5-35869818;