NM_002185.5:c.*2841T>C

Variant names:

• chr5-35879327-T-C
• rs1053496
• NM_002185.5:c.*2841T>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.*2841T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 232,448 control chromosomes in the GnomAD database, including 10,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8137 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2743 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.790
• Publications: 14 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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=-0.81).
• BP6: Variant 5-35879327-T-C is Benign according to our data. Variant chr5-35879327-T-C is described in ClinVar as Benign. ClinVar VariationId is 906321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 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.*2841T>C		3_prime_UTR	Exon 8 of 8	NP_002176.2
	IL7R	NM_001437964.1		c.*3719T>C		3_prime_UTR	Exon 7 of 7	NP_001424893.1
	IL7R	NM_001410734.1		c.*3338T>C		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.*2841T>C		3_prime_UTR	Exon 8 of 8	ENSP00000306157.3	P16871-1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47138 AN: 151968 Hom.: 8135 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0739

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.248 AC: 19903 AN: 80362 Hom.: 2743 Cov.: 0 AF XY: 0.247 AC XY: 9137 AN XY: 36964

African (AFR) AF: 0.452 AC: 1748 AN: 3866

American (AMR) AF: 0.208 AC: 512 AN: 2462

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 1407 AN: 5086

East Asian (EAS) AF: 0.0758 AC: 858 AN: 11320

South Asian (SAS) AF: 0.197 AC: 137 AN: 694

European-Finnish (FIN) AF: 0.333 AC: 20 AN: 60

Middle Eastern (MID) AF: 0.318 AC: 155 AN: 488

European-Non Finnish (NFE) AF: 0.267 AC: 13285 AN: 49664

Other (OTH) AF: 0.265 AC: 1781 AN: 6722

GnomAD4 genome AF: 0.310 AC: 47161 AN: 152086 Hom.: 8137 Cov.: 32 AF XY: 0.307 AC XY: 22845 AN XY: 74364

African (AFR) AF: 0.457 AC: 18930 AN: 41450

American (AMR) AF: 0.233 AC: 3567 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3472

East Asian (EAS) AF: 0.0743 AC: 385 AN: 5182

South Asian (SAS) AF: 0.199 AC: 961 AN: 4820

European-Finnish (FIN) AF: 0.289 AC: 3053 AN: 10576

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

European-Non Finnish (NFE) AF: 0.269 AC: 18305 AN: 67980

Other (OTH) AF: 0.303 AC: 640 AN: 2112

Alfa AF: 0.278 Hom.: 2863

Bravo AF: 0.312

Asia WGS AF: 0.163 AC: 568 AN: 3478

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	-0.81
CADD	Benign	0.54
DANN	Benign	0.70
PhyloP100		-0.79
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: rs1053496; hg19: chr5-35879429;