NM_144701.3:c.929T>C

Variant names:

• chr1-67219704-T-C
• rs7530511
• NM_144701.3:c.929T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144701.3(IL23R):​c.929T>C​(p.Leu310Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,613,024 control chromosomes in the GnomAD database, including 621,497 homozygotes. 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 Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. L310L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.85 (55026 hom., cov: 31)
  • Exomes 𝑓: 0.88 (566471 hom.)
• Consequence: IL23R NM_144701.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.37
• Publications: 117 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.2443993E-7).
• BP6: Variant 1-67219704-T-C is Benign according to our data. Variant chr1-67219704-T-C is described in ClinVar as Benign. ClinVar VariationId is 1169786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144701.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.929T>C	p.Leu310Pro	missense	Exon 7 of 11	NP_653302.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.929T>C	p.Leu310Pro	missense	Exon 7 of 11	ENSP00000321345.5	Q5VWK5-1
	IL23R	ENST00000425614.3	TSL:1	c.164T>C	p.Leu55Pro	missense	Exon 2 of 6	ENSP00000387640.2	Q5VWK5-6
	IL23R	ENST00000473881.2	TSL:1	n.164T>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000486667.1	A0A0D9SFJ7

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128970 AN: 152018 Hom.: 54990 Cov.: 31

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.848

GnomAD2 exomes AF: 0.883 AC: 221943 AN: 251350 AF XY: 0.886

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.897

Gnomad EAS exome AF: 0.986

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.879

GnomAD4 exome AF: 0.880 AC: 1285433 AN: 1460888 Hom.: 566471 Cov.: 46 AF XY: 0.881 AC XY: 640508 AN XY: 726824

African (AFR) AF: 0.763 AC: 25500 AN: 33440

American (AMR) AF: 0.906 AC: 40522 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 23419 AN: 26132

East Asian (EAS) AF: 0.987 AC: 39180 AN: 39694

South Asian (SAS) AF: 0.932 AC: 80370 AN: 86250

European-Finnish (FIN) AF: 0.841 AC: 44923 AN: 53408

Middle Eastern (MID) AF: 0.864 AC: 4980 AN: 5762

European-Non Finnish (NFE) AF: 0.876 AC: 973363 AN: 1111110

Other (OTH) AF: 0.881 AC: 53176 AN: 60370

GnomAD4 genome AF: 0.848 AC: 129061 AN: 152136 Hom.: 55026 Cov.: 31 AF XY: 0.850 AC XY: 63210 AN XY: 74340

African (AFR) AF: 0.769 AC: 31934 AN: 41510

American (AMR) AF: 0.870 AC: 13288 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3129 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5097 AN: 5170

South Asian (SAS) AF: 0.934 AC: 4492 AN: 4810

European-Finnish (FIN) AF: 0.856 AC: 9052 AN: 10574

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59183 AN: 68004

Other (OTH) AF: 0.849 AC: 1794 AN: 2114

Alfa AF: 0.866 Hom.: 218510

Bravo AF: 0.846

TwinsUK AF: 0.881 AC: 3266

ALSPAC AF: 0.881 AC: 3397

ESP6500AA AF: 0.763 AC: 3361

ESP6500EA AF: 0.870 AC: 7486

ExAC AF: 0.878 AC: 106554

Asia WGS AF: 0.958 AC: 3332 AN: 3478

EpiCase AF: 0.880

EpiControl AF: 0.878

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.035
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.066
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.00073	N
LIST_S2	Benign	0.090	T
MetaRNN	Benign	7.2e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.7	N
PhyloP100		2.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.19
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.079
MPC		0.27
ClinPred		0.0030	T
GERP RS		4.9
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.31
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7530511; hg19: chr1-67685387; COSMIC: COSV107419264;