NM_002185.5:c.82+16G>C

Variant names:

• chr5-35857075-G-C
• rs1353252
• NM_002185.5:c.82+16G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002185.5(IL7R):​c.82+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,504,278 control chromosomes in the GnomAD database, including 335,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39202 hom., cov: 31)
  • Exomes 𝑓: 0.66 (295827 hom.)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.54
• Publications: 21 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-35857075-G-C is Benign according to our data. Variant chr5-35857075-G-C is described in ClinVar as Benign. ClinVar VariationId is 258579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 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.82+16G>C		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.82+16G>C		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.82+16G>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.82+16G>C		intron	N/A	ENSP00000306157.3	P16871-1
	IL7R	ENST00000877114.1		c.82+16G>C		intron	N/A	ENSP00000547173.1
	IL7R	ENST00000506850.5	TSL:2	c.82+16G>C		intron	N/A	ENSP00000421207.1	P16871-3

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107499 AN: 151956 Hom.: 39184 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.678

GnomAD2 exomes AF: 0.627 AC: 155530 AN: 248058 AF XY: 0.625

Gnomad AFR exome AF: 0.879

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.731

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.657 AC: 888434 AN: 1352202 Hom.: 295827 Cov.: 21 AF XY: 0.653 AC XY: 443204 AN XY: 678930

African (AFR) AF: 0.880 AC: 27474 AN: 31212

American (AMR) AF: 0.512 AC: 22835 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 16033 AN: 25488

East Asian (EAS) AF: 0.421 AC: 16496 AN: 39168

South Asian (SAS) AF: 0.516 AC: 43460 AN: 84208

European-Finnish (FIN) AF: 0.732 AC: 38146 AN: 52136

Middle Eastern (MID) AF: 0.610 AC: 3417 AN: 5598

European-Non Finnish (NFE) AF: 0.675 AC: 683446 AN: 1012940

Other (OTH) AF: 0.653 AC: 37127 AN: 56854

GnomAD4 genome AF: 0.707 AC: 107565 AN: 152076 Hom.: 39202 Cov.: 31 AF XY: 0.702 AC XY: 52165 AN XY: 74322

African (AFR) AF: 0.872 AC: 36196 AN: 41498

American (AMR) AF: 0.574 AC: 8767 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2212 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2155 AN: 5172

South Asian (SAS) AF: 0.511 AC: 2461 AN: 4820

European-Finnish (FIN) AF: 0.735 AC: 7749 AN: 10536

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45682 AN: 67980

Other (OTH) AF: 0.676 AC: 1429 AN: 2114

Alfa AF: 0.625 Hom.: 3663

Bravo AF: 0.706

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 104 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.8
DANN	Benign	0.60
PhyloP100		-1.5
PromoterAI		0.039	Neutral
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: rs1353252; hg19: chr5-35857177; COSMIC: COSV57406102;