rs202007062

Variant names:

• chr5-35857053-C-A
• NM_002185.5:c.76C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-35857053-C-A
• chr5-35857053-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002185.5(IL7R):​c.76C>A​(p.Gln26Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11951575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.76C>A	p.Gln26Lys	missense_variant	Exon 1 of 8	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.76C>A	p.Gln26Lys	missense_variant	Exon 1 of 8	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438784 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 717400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.16	.;.;T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.67	T;T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	.;.;M;M;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	N;D;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.19	T;T;T;T;T
Sift4G	Uncertain	0.028	D;D;T;T;D
Polyphen		0.024	.;.;B;.;.
Vest4		0.10, 0.12, 0.18
MutPred		0.29		Gain of ubiquitination at Q26 (P = 0.0048);Gain of ubiquitination at Q26 (P = 0.0048);Gain of ubiquitination at Q26 (P = 0.0048);Gain of ubiquitination at Q26 (P = 0.0048);Gain of ubiquitination at Q26 (P = 0.0048);
MVP		0.87
MPC		0.020
ClinPred		0.12	T
GERP RS		3.6
Varity_R		0.13
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-35857155;