rs10491435

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-35877739-G-A
• chr5-35877739-G-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>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 0.273 in 233,064 control chromosomes in the GnomAD database, including 9,403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6799 hom., cov: 32)
  • Exomes 𝑓: 0.24 (2604 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: 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=-0.87).
• BP6: Variant 5-35877739-G-A is Benign according to our data. Variant chr5-35877739-G-A is described in ClinVar as Benign. ClinVar VariationId is 353288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 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.*1253G>A		3_prime_UTR	Exon 8 of 8	NP_002176.2
	IL7R	NR_120485.3		n.2457G>A		non_coding_transcript_exon	Exon 6 of 6
	IL7R	NM_001437964.1		c.*2131G>A		3_prime_UTR	Exon 7 of 7	NP_001424893.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43893 AN: 151982 Hom.: 6798 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.243 AC: 19653 AN: 80964 Hom.: 2604 Cov.: 0 AF XY: 0.243 AC XY: 9049 AN XY: 37210

African (AFR) AF: 0.372 AC: 1449 AN: 3900

American (AMR) AF: 0.202 AC: 505 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 1416 AN: 5124

East Asian (EAS) AF: 0.0760 AC: 867 AN: 11410

South Asian (SAS) AF: 0.199 AC: 140 AN: 702

European-Finnish (FIN) AF: 0.300 AC: 18 AN: 60

Middle Eastern (MID) AF: 0.311 AC: 153 AN: 492

European-Non Finnish (NFE) AF: 0.268 AC: 13383 AN: 50008

Other (OTH) AF: 0.254 AC: 1722 AN: 6768

GnomAD4 genome AF: 0.289 AC: 43897 AN: 152100 Hom.: 6799 Cov.: 32 AF XY: 0.286 AC XY: 21266 AN XY: 74358

African (AFR) AF: 0.382 AC: 15846 AN: 41470

American (AMR) AF: 0.226 AC: 3457 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.0727 AC: 377 AN: 5188

South Asian (SAS) AF: 0.199 AC: 957 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3047 AN: 10552

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

European-Non Finnish (NFE) AF: 0.269 AC: 18296 AN: 68004

Other (OTH) AF: 0.281 AC: 594 AN: 2116

Alfa AF: 0.190 Hom.: 494

Bravo AF: 0.298

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	2.2
DANN	Benign	0.59
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

Other links and lift over

dbSNP: rs10491435; hg19: chr5-35877841;