chr1-67219760-G-A

Variant names:

• chr1-67219760-G-A
• rs7518660
• NM_144701.3:c.955+30G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144701.3(IL23R):​c.955+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,594,142 control chromosomes in the GnomAD database, including 163,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16500 hom., cov: 32)
  • Exomes 𝑓: 0.45 (147202 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 1-67219760-G-A is Benign according to our data. Variant chr1-67219760-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.955+30G>A		intron	N/A	NP_653302.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.955+30G>A		intron	N/A	ENSP00000321345.5
	IL23R	ENST00000425614.3	TSL:1	c.190+30G>A		intron	N/A	ENSP00000387640.2
	IL23R	ENST00000473881.2	TSL:1	n.190+30G>A		intron	N/A	ENSP00000486667.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70030 AN: 151840 Hom.: 16492 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.436

GnomAD2 exomes AF: 0.434 AC: 108634 AN: 250042 AF XY: 0.423

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.578

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.423

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.447 AC: 644302 AN: 1442182 Hom.: 147202 Cov.: 29 AF XY: 0.441 AC XY: 316687 AN XY: 718786

African (AFR) AF: 0.478 AC: 15830 AN: 33098

American (AMR) AF: 0.568 AC: 25393 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11106 AN: 26000

East Asian (EAS) AF: 0.271 AC: 10731 AN: 39594

South Asian (SAS) AF: 0.289 AC: 24851 AN: 85936

European-Finnish (FIN) AF: 0.431 AC: 22948 AN: 53264

Middle Eastern (MID) AF: 0.350 AC: 2006 AN: 5734

European-Non Finnish (NFE) AF: 0.462 AC: 505368 AN: 1094120

Other (OTH) AF: 0.436 AC: 26069 AN: 59756

GnomAD4 genome AF: 0.461 AC: 70079 AN: 151960 Hom.: 16500 Cov.: 32 AF XY: 0.457 AC XY: 33943 AN XY: 74242

African (AFR) AF: 0.488 AC: 20240 AN: 41438

American (AMR) AF: 0.534 AC: 8160 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1483 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1337 AN: 5158

South Asian (SAS) AF: 0.279 AC: 1344 AN: 4810

European-Finnish (FIN) AF: 0.434 AC: 4584 AN: 10552

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31512 AN: 67944

Other (OTH) AF: 0.436 AC: 921 AN: 2112

Alfa AF: 0.464 Hom.: 25897

Bravo AF: 0.474

Asia WGS AF: 0.333 AC: 1160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0050
DANN	Benign	0.17
PhyloP100		-2.4
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs7518660; hg19: chr1-67685443; COSMIC: COSV61374534;