NM_005535.3:c.1972T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005535.3(IL12RB1):​c.1972T>G​(p.Cys658Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 147,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C658R) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000068 ( 0 hom., cov: 31)

Consequence

IL12RB1
NM_005535.3 missense

Scores

1
1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46
Variant links:
Genes affected
IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.063851595).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL12RB1NM_005535.3 linkc.1972T>G p.Cys658Gly missense_variant Exon 16 of 17 ENST00000593993.7 NP_005526.1 P42701-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL12RB1ENST00000593993.7 linkc.1972T>G p.Cys658Gly missense_variant Exon 16 of 17 1 NM_005535.3 ENSP00000472165.2 P42701-1
IL12RB1ENST00000600835.6 linkc.1972T>G p.Cys658Gly missense_variant Exon 17 of 18 1 ENSP00000470788.1 P42701-1

Frequencies

GnomAD3 genomes
AF:
0.00000677
AC:
1
AN:
147654
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000677
AC:
1
AN:
147654
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
71924
show subpopulations
Gnomad4 AFR
AF:
0.0000257
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
0.92
DANN
Benign
0.84
DEOGEN2
Benign
0.079
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.38
.;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.064
T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Benign
0.33
T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0010
B;B
Vest4
0.22
MutPred
0.25
Loss of stability (P = 0.0075);Loss of stability (P = 0.0075);
MVP
0.36
MPC
0.13
ClinPred
0.13
T
GERP RS
0.67
Varity_R
0.45
gMVP
0.14

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: chr19-18170715; API