chr1-67182777-T-C

Position:

• chr1-67182777-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144701.3(IL23R):​c.368-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,605,410 control chromosomes in the GnomAD database, including 640,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.91 (63787 hom., cov: 32)
  • Exomes 𝑓: 0.89 (576622 hom.)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-67182777-T-C is Benign according to our data. Variant chr1-67182777-T-C is described in ClinVar as [Benign]. Clinvar id is 2688370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	NM_144701.3	c.368-59T>C		intron_variant		ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.368-59T>C		intron_variant			XP_011539092.1
IL23R	XM_011540791.4	c.368-59T>C		intron_variant			XP_011539093.1
IL23R	XM_047447227.1	c.368-59T>C		intron_variant			XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.368-59T>C		intron_variant		1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139042 AN: 152154 Hom.: 63727 Cov.: 32

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.883

GnomAD4 exome AF: 0.890 AC: 1293627 AN: 1453138 Hom.: 576622 AF XY: 0.891 AC XY: 644151 AN XY: 723232

Gnomad4 AFR exome AF: 0.982

Gnomad4 AMR exome AF: 0.932

Gnomad4 ASJ exome AF: 0.865

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.943

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 0.895

GnomAD4 genome AF: 0.914 AC: 139160 AN: 152272 Hom.: 63787 Cov.: 32 AF XY: 0.913 AC XY: 67973 AN XY: 74464

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.884

Alfa AF: 0.887 Hom.: 33964

Bravo AF: 0.920

Asia WGS AF: 0.975 AC: 3391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.11

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: rs6687620; hg19: chr1-67648460;