5-35877739-G-T

Variant names:

• chr5-35877739-G-T
• rs10491435
• NM_002185.5:c.*1253G>T

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.*1253G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 233,124 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene IL7R is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.022 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (16 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.130
• Publications: 7 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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

Specifications for IL7R are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-35877739-G-T is Benign according to our data. Variant chr5-35877739-G-T is described in ClinVar as Benign. ClinVar VariationId is 353289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 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.*1253G>T		3_prime_UTR	Exon 8 of 8	NP_002176.2
	IL7R	NM_001437964.1		c.*2131G>T		3_prime_UTR	Exon 7 of 7	NP_001424893.1
	IL7R	NM_001410734.1		c.*1750G>T		3_prime_UTR	Exon 7 of 7	NP_001397663.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.*1253G>T		3_prime_UTR	Exon 8 of 8	ENSP00000306157.3	P16871-1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3263 AN: 152034 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00747

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.00524 AC: 424 AN: 80972 Hom.: 16 Cov.: 0 AF XY: 0.00457 AC XY: 170 AN XY: 37212

African (AFR) AF: 0.0813 AC: 317 AN: 3900

American (AMR) AF: 0.00800 AC: 20 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5124

East Asian (EAS) AF: 0.00 AC: 0 AN: 11410

South Asian (SAS) AF: 0.00 AC: 0 AN: 702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 60

Middle Eastern (MID) AF: 0.00407 AC: 2 AN: 492

European-Non Finnish (NFE) AF: 0.000240 AC: 12 AN: 50014

Other (OTH) AF: 0.0108 AC: 73 AN: 6770

GnomAD4 genome AF: 0.0216 AC: 3283 AN: 152152 Hom.: 115 Cov.: 32 AF XY: 0.0213 AC XY: 1588 AN XY: 74390

African (AFR) AF: 0.0747 AC: 3098 AN: 41488

American (AMR) AF: 0.00746 AC: 114 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68016

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.00 Hom.: 494

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 104 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.90
DANN	Benign	0.65
PhyloP100		-0.13
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10491435;

hg19: chr5-35877841;