chr5-35857105-C-T

Variant names:

• chr5-35857105-C-T
• rs1353251
• NM_002185.5:c.82+46C>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.82+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,209,236 control chromosomes in the GnomAD database, including 38,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3936 hom., cov: 32)
  • Exomes 𝑓: 0.24 (34974 hom.)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.15
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-35857105-C-T is Benign according to our data. Variant chr5-35857105-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 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.82+46C>T		intron	N/A	NP_002176.2
	IL7R	NM_001437964.1		c.82+46C>T		intron	N/A	NP_001424893.1
	IL7R	NM_001410734.1		c.82+46C>T		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.82+46C>T		intron	N/A	ENSP00000306157.3
	IL7R	ENST00000506850.5	TSL:2	c.82+46C>T		intron	N/A	ENSP00000421207.1
	IL7R	ENST00000511982.1	TSL:2	c.82+46C>T		intron	N/A	ENSP00000425309.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29068 AN: 151986 Hom.: 3928 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.274 AC: 67498 AN: 246504 AF XY: 0.273

Gnomad AFR exome AF: 0.0408

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.238 AC: 251104 AN: 1057132 Hom.: 34974 Cov.: 14 AF XY: 0.242 AC XY: 131678 AN XY: 545176

African (AFR) AF: 0.0396 AC: 1014 AN: 25576

American (AMR) AF: 0.431 AC: 19055 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4488 AN: 23690

East Asian (EAS) AF: 0.522 AC: 19737 AN: 37802

South Asian (SAS) AF: 0.382 AC: 29863 AN: 78156

European-Finnish (FIN) AF: 0.178 AC: 8885 AN: 49936

Middle Eastern (MID) AF: 0.201 AC: 1015 AN: 5052

European-Non Finnish (NFE) AF: 0.209 AC: 156081 AN: 745580

Other (OTH) AF: 0.233 AC: 10966 AN: 47102

GnomAD4 genome AF: 0.191 AC: 29082 AN: 152104 Hom.: 3936 Cov.: 32 AF XY: 0.198 AC XY: 14694 AN XY: 74334

African (AFR) AF: 0.0446 AC: 1850 AN: 41508

American (AMR) AF: 0.340 AC: 5192 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3472

East Asian (EAS) AF: 0.526 AC: 2716 AN: 5166

South Asian (SAS) AF: 0.398 AC: 1913 AN: 4808

European-Finnish (FIN) AF: 0.177 AC: 1872 AN: 10570

Middle Eastern (MID) AF: 0.208 AC: 60 AN: 288

European-Non Finnish (NFE) AF: 0.210 AC: 14296 AN: 67992

Other (OTH) AF: 0.212 AC: 449 AN: 2116

Alfa AF: 0.206 Hom.: 2142

Bravo AF: 0.194

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.35
PhyloP100		-1.1
PromoterAI		-0.0055	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: rs1353251; hg19: chr5-35857207; COSMIC: COSV57405402;