1-67219704-T-C

Position:

• chr1-67219704-T-C

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.929T>C	p.Leu310Pro	missense_variant	7/11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.929T>C	p.Leu310Pro	missense_variant	7/11		XP_011539092.1
IL23R	XM_011540791.4	c.929T>C	p.Leu310Pro	missense_variant	7/11		XP_011539093.1
IL23R	XM_047447227.1	c.929T>C	p.Leu310Pro	missense_variant	7/11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.929T>C	p.Leu310Pro	missense_variant	7/11	1	NM_144701.3	ENSP00000321345.5

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

GnomAD3 exomes AF: 0.883 AC: 221943 AN: 251350 Hom.: 98314 AF XY: 0.886 AC XY: 120288 AN XY: 135838

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 SAS exome AF: 0.933

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

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.906

Gnomad4 ASJ exome AF: 0.896

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.841

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.881

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

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.849

Alfa AF: 0.871 Hom.: 146681

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 88. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

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;T;T
MetaRNN	Benign	7.2e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.7	.;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	3.7	.;N;.
REVEL	Benign	0.19
Sift	Benign	1.0	.;T;.
Sift4G	Benign	1.0	.;T;T
Polyphen		0.0	.;B;B
Vest4		0.079, 0.034
MPC		0.27
ClinPred		0.0030	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs7530511; hg19: chr1-67685387;