NM_002185.5:c.706+122T>G

Variant names:

• chr5-35873770-T-G
• rs1494554
• NM_002185.5:c.706+122T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002185.5(IL7R):​c.706+122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 876,188 control chromosomes in the GnomAD database, including 29,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5945 hom., cov: 32)
  • Exomes 𝑓: 0.25 (23914 hom.)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.209
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-35873770-T-G is Benign according to our data. Variant chr5-35873770-T-G is described in ClinVar as Benign. ClinVar VariationId is 1183897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.706+122T>G		intron_variant	Intron 5 of 7	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.706+122T>G		intron_variant	Intron 5 of 7	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41347 AN: 151978 Hom.: 5944 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.250 AC: 180812 AN: 724092 Hom.: 23914 AF XY: 0.249 AC XY: 96432 AN XY: 386632

African (AFR) AF: 0.320 AC: 6059 AN: 18928

American (AMR) AF: 0.159 AC: 6548 AN: 41108

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 5791 AN: 21314

East Asian (EAS) AF: 0.0710 AC: 2514 AN: 35390

South Asian (SAS) AF: 0.207 AC: 14322 AN: 69210

European-Finnish (FIN) AF: 0.294 AC: 14961 AN: 50896

Middle Eastern (MID) AF: 0.294 AC: 820 AN: 2788

European-Non Finnish (NFE) AF: 0.269 AC: 120824 AN: 448462

Other (OTH) AF: 0.249 AC: 8973 AN: 35996

GnomAD4 genome AF: 0.272 AC: 41349 AN: 152096 Hom.: 5945 Cov.: 32 AF XY: 0.270 AC XY: 20054 AN XY: 74378

African (AFR) AF: 0.324 AC: 13437 AN: 41486

American (AMR) AF: 0.220 AC: 3356 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3470

East Asian (EAS) AF: 0.0728 AC: 377 AN: 5182

South Asian (SAS) AF: 0.199 AC: 958 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3054 AN: 10568

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

European-Non Finnish (NFE) AF: 0.269 AC: 18278 AN: 67970

Other (OTH) AF: 0.268 AC: 567 AN: 2116

Alfa AF: 0.194 Hom.: 525

Bravo AF: 0.267

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.45
PhyloP100		0.21
PromoterAI		0.014	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: rs1494554; hg19: chr5-35873872; COSMIC: COSV57415459; COSMIC: COSV57415459;