5-35877403-G-A

Variant names:

• chr5-35877403-G-A
• rs10063294
• NM_002185.5:c.*917G>A

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.*917G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 232,890 control chromosomes in the GnomAD database, including 37,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26489 hom., cov: 31)
  • Exomes 𝑓: 0.50 (10571 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.218
• Publications: 24 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=-0.84).
• BP6: Variant 5-35877403-G-A is Benign according to our data. Variant chr5-35877403-G-A is described in ClinVar as Benign. ClinVar VariationId is 353284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 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.*917G>A		3_prime_UTR	Exon 8 of 8	NP_002176.2
	IL7R	NM_001437964.1		c.*1795G>A		3_prime_UTR	Exon 7 of 7	NP_001424893.1
	IL7R	NM_001410734.1		c.*1414G>A		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.*917G>A		3_prime_UTR	Exon 8 of 8	ENSP00000306157.3	P16871-1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87742 AN: 151914 Hom.: 26464 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.501 AC: 40524 AN: 80858 Hom.: 10571 Cov.: 0 AF XY: 0.501 AC XY: 18612 AN XY: 37160

African (AFR) AF: 0.744 AC: 2895 AN: 3890

American (AMR) AF: 0.408 AC: 1019 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 2622 AN: 5112

East Asian (EAS) AF: 0.306 AC: 3484 AN: 11402

South Asian (SAS) AF: 0.454 AC: 318 AN: 700

European-Finnish (FIN) AF: 0.638 AC: 37 AN: 58

Middle Eastern (MID) AF: 0.494 AC: 243 AN: 492

European-Non Finnish (NFE) AF: 0.528 AC: 26383 AN: 49944

Other (OTH) AF: 0.521 AC: 3523 AN: 6760

GnomAD4 genome AF: 0.578 AC: 87813 AN: 152032 Hom.: 26489 Cov.: 31 AF XY: 0.576 AC XY: 42768 AN XY: 74306

African (AFR) AF: 0.746 AC: 30924 AN: 41474

American (AMR) AF: 0.431 AC: 6581 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1422 AN: 5178

South Asian (SAS) AF: 0.448 AC: 2156 AN: 4808

European-Finnish (FIN) AF: 0.636 AC: 6712 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36405 AN: 67964

Other (OTH) AF: 0.529 AC: 1114 AN: 2106

Alfa AF: 0.540 Hom.: 42231

Bravo AF: 0.569

Asia WGS AF: 0.431 AC: 1499 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	-0.84
CADD	Benign	7.0
DANN	Benign	0.64
PhyloP100		0.22
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: rs10063294; hg19: chr5-35877505;