Genetic Variant NM_144701.3:c.1084G>T (chr1-67240217-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144701.3(IL23R):c.1084G>T(p.Val362Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V362I) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IL23R
NM_144701.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.808

Publications

40 publications found

Variant links:

Genes affected

IL23R (HGNC:19100): (interleukin 23 receptor) The protein encoded by this gene is a subunit of the receptor for IL23A/IL23. This protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner. [provided by RefSeq, Jul 2008]

IL23R links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024895936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3 link	c.1084G>T	p.Val362Phe	missense_variant	Exon 9 of 11	ENST00000347310.10	NP_653302.2	Q5VWK5-1
IL23R	XM_011540790.4 link	c.1084G>T	p.Val362Phe	missense_variant	Exon 9 of 11		XP_011539092.1	Q5VWK5-1
IL23R	XM_011540791.4 link	c.1084G>T	p.Val362Phe	missense_variant	Exon 9 of 11		XP_011539093.1	Q5VWK5-1
IL23R	XM_047447227.1 link	c.1084G>T	p.Val362Phe	missense_variant	Exon 9 of 11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10 link	c.1084G>T	p.Val362Phe	missense_variant	Exon 9 of 11	1	NM_144701.3	ENSP00000321345.5		Q5VWK5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460676

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111036

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.018

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.059

.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

.;N;.

PhyloP100

-0.81

PrimateAI

Benign

0.30

PROVEAN

Benign

0.24

.;N;.

REVEL

Benign

0.27

Sift

Benign

0.88

.;T;.

Sift4G

Benign

0.71

.;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.42, 0.18

MutPred

0.24

.;Loss of sheet (P = 0.0357);.;

MVP

0.23

MPC

0.22

ClinPred

0.062

GERP RS

-6.2

Varity_R

0.051

gMVP

0.36

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over