rs11567764

Variant names:

• chr5-35873503-G-A
• rs11567764
• NM_002185.5:c.561G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-35873503-G-A
• chr5-35873503-G-C
• chr5-35873503-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002185.5(IL7R):​c.561G>A​(p.Lys187Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,613,958 control chromosomes in the GnomAD database, including 649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (318 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (331 hom.)
• Consequence: IL7R NM_002185.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.798
• Publications: 10 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-35873503-G-A is Benign according to our data. Variant chr5-35873503-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.798 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 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.561G>A	p.Lys187Lys	synonymous	Exon 5 of 8	NP_002176.2
	IL7R	NM_001437964.1		c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 7	NP_001424893.1
	IL7R	NM_001410734.1		c.561G>A	p.Lys187Lys	synonymous	Exon 5 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.561G>A	p.Lys187Lys	synonymous	Exon 5 of 8	ENSP00000306157.3	P16871-1
	IL7R	ENST00000877114.1		c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 7	ENSP00000547173.1
	IL7R	ENST00000506850.5	TSL:2	c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 6	ENSP00000421207.1	P16871-3

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5468 AN: 152138 Hom.: 313 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0316

GnomAD2 exomes AF: 0.00953 AC: 2390 AN: 250744 AF XY: 0.00674

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.00593

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000283

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00379 AC: 5547 AN: 1461702 Hom.: 331 Cov.: 30 AF XY: 0.00324 AC XY: 2357 AN XY: 727166

African (AFR) AF: 0.134 AC: 4486 AN: 33436

American (AMR) AF: 0.00655 AC: 293 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5766

European-Non Finnish (NFE) AF: 0.000148 AC: 165 AN: 1111912

Other (OTH) AF: 0.00881 AC: 532 AN: 60384

GnomAD4 genome AF: 0.0361 AC: 5498 AN: 152256 Hom.: 318 Cov.: 32 AF XY: 0.0346 AC XY: 2573 AN XY: 74442

African (AFR) AF: 0.126 AC: 5216 AN: 41520

American (AMR) AF: 0.0118 AC: 181 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68038

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.00710 Hom.: 44

Bravo AF: 0.0416

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 104 (2)
-	-	1	IL7R-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		0.80
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs11567764; hg19: chr5-35873605; COSMIC: COSV57406853;