5-35860921-C-G

Variant names:

• chr5-35860921-C-G
• rs138482569
• NM_002185.5:c.152C>G

Variant summary

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

The NM_002185.5(IL7R):​c.152C>G​(p.Ser51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S51S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IL7R NM_002185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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=0.22142324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.152C>G	p.Ser51Trp	missense_variant	Exon 2 of 8	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.152C>G	p.Ser51Trp	missense_variant	Exon 2 of 8	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251152 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135712

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460898 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726870

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.69	.;.;D;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.86	D;T;D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	.;.;L;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.1	D;D;D;N;D
REVEL	Uncertain	0.35
Sift	Benign	0.041	D;T;D;D;D
Sift4G	Benign	0.14	T;T;D;T;T
Polyphen		1.0	.;.;D;.;.
Vest4		0.35, 0.34, 0.39
MutPred		0.40		Loss of disorder (P = 0.0017);Loss of disorder (P = 0.0017);Loss of disorder (P = 0.0017);Loss of disorder (P = 0.0017);Loss of disorder (P = 0.0017);
MVP		0.87
MPC		0.097
ClinPred		0.61	D
GERP RS		-0.80
Varity_R		0.12
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs138482569; hg19: chr5-35861023;