chr1-67200769-C-A

Variant names:

• chr1-67200769-C-A
• rs11465797
• NM_144701.3:c.524C>A

Variant summary

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

The NM_144701.3(IL23R):​c.524C>A​(p.Thr175Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL23R NM_144701.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

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]

C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

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=0.1839079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.524C>A	p.Thr175Asn	missense_variant	Exon 5 of 11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.524C>A	p.Thr175Asn	missense_variant	Exon 5 of 11		XP_011539092.1
IL23R	XM_011540791.4	c.524C>A	p.Thr175Asn	missense_variant	Exon 5 of 11		XP_011539093.1
IL23R	XM_047447227.1	c.524C>A	p.Thr175Asn	missense_variant	Exon 5 of 11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.524C>A	p.Thr175Asn	missense_variant	Exon 5 of 11	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.028
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.24	T
Sift4G	Uncertain	0.015	D
Polyphen		0.63	P
Vest4		0.16
MutPred		0.24		Gain of sheet (P = 0.0827);
MVP		0.55
MPC		0.67
ClinPred		0.45	T
GERP RS		6.0
Varity_R		0.32
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11465797; hg19: chr1-67666452;