rs7539625

Variant names:

• chr1-67207082-G-A
• rs7539625
• NM_144701.3:c.798+27G>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.798+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,608,758 control chromosomes in the GnomAD database, including 87,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7447 hom., cov: 31)
  • Exomes 𝑓: 0.32 (79669 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0500
• Publications: 28 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=-0.8).
• BP6: Variant 1-67207082-G-A is Benign according to our data. Variant chr1-67207082-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.798+27G>A		intron_variant	Intron 6 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.798+27G>A		intron_variant	Intron 6 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.798+27G>A		intron_variant	Intron 6 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.798+27G>A		intron_variant	Intron 6 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.798+27G>A		intron_variant	Intron 6 of 10	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45978 AN: 151852 Hom.: 7442 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.326 AC: 81869 AN: 250800 AF XY: 0.343

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.527

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.320 AC: 466114 AN: 1456788 Hom.: 79669 Cov.: 33 AF XY: 0.328 AC XY: 238091 AN XY: 725012

African (AFR) AF: 0.303 AC: 10112 AN: 33352

American (AMR) AF: 0.164 AC: 7351 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8848 AN: 26100

East Asian (EAS) AF: 0.532 AC: 21085 AN: 39604

South Asian (SAS) AF: 0.555 AC: 47744 AN: 86090

European-Finnish (FIN) AF: 0.251 AC: 13382 AN: 53326

Middle Eastern (MID) AF: 0.444 AC: 2550 AN: 5744

European-Non Finnish (NFE) AF: 0.302 AC: 334855 AN: 1107658

Other (OTH) AF: 0.335 AC: 20187 AN: 60202

GnomAD4 genome AF: 0.303 AC: 46003 AN: 151970 Hom.: 7447 Cov.: 31 AF XY: 0.305 AC XY: 22655 AN XY: 74308

African (AFR) AF: 0.296 AC: 12284 AN: 41464

American (AMR) AF: 0.211 AC: 3218 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3466

East Asian (EAS) AF: 0.530 AC: 2745 AN: 5176

South Asian (SAS) AF: 0.564 AC: 2717 AN: 4814

European-Finnish (FIN) AF: 0.263 AC: 2771 AN: 10520

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20063 AN: 67944

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.298 Hom.: 27568

Bravo AF: 0.292

Asia WGS AF: 0.485 AC: 1683 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 39% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.47
PhyloP100		0.050
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: rs7539625; hg19: chr1-67672765; COSMIC: COSV61374831; COSMIC: COSV61374831;