chr1-67169369-A-G

Position:

• chr1-67169369-A-G

Variant summary

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

The NM_144701.3(IL23R):​c.98A>G​(p.His33Arg) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H33H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL23R NM_144701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.225

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=0.07928416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL23R	NM_144701.3	c.98A>G	p.His33Arg	missense_variant	3/11	ENST00000347310.10
IL23R	XM_011540790.4	c.98A>G	p.His33Arg	missense_variant	3/11
IL23R	XM_011540791.4	c.98A>G	p.His33Arg	missense_variant	3/11
IL23R	XM_047447227.1	c.98A>G	p.His33Arg	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL23R	ENST00000347310.10	c.98A>G	p.His33Arg	missense_variant	3/11	1	NM_144701.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.98A>G (p.H33R) alteration is located in exon 3 (coding exon 2) of the IL23R gene. This alteration results from a A to G substitution at nucleotide position 98, causing the histidine (H) at amino acid position 33 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.8
DANN	Benign	0.76
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.16
Sift	Benign	0.53	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.60		Gain of sheet (P = 0.0827);
MVP		0.53
MPC		0.56
ClinPred		0.057	T
GERP RS		-3.4
Varity_R		0.18
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67635052;