chr1-67182777-T-C

Variant names:

• chr1-67182777-T-C
• rs6687620
• NM_144701.3:c.368-59T>C

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.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
• 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=-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 VariationId 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 rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.368-59T>C		intron_variant	Intron 3 of 10	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.368-59T>C		intron_variant	Intron 3 of 10		XP_011539092.1
IL23R	XM_011540791.4	c.368-59T>C		intron_variant	Intron 3 of 10		XP_011539093.1
IL23R	XM_047447227.1	c.368-59T>C		intron_variant	Intron 3 of 10		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.368-59T>C		intron_variant	Intron 3 of 10	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

African (AFR) AF: 0.982 AC: 32709 AN: 33320

American (AMR) AF: 0.932 AC: 41537 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 22448 AN: 25954

East Asian (EAS) AF: 0.997 AC: 39310 AN: 39426

South Asian (SAS) AF: 0.943 AC: 80782 AN: 85646

European-Finnish (FIN) AF: 0.851 AC: 44811 AN: 52640

Middle Eastern (MID) AF: 0.858 AC: 4932 AN: 5748

European-Non Finnish (NFE) AF: 0.880 AC: 973392 AN: 1105844

Other (OTH) AF: 0.895 AC: 53706 AN: 59992

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

African (AFR) AF: 0.979 AC: 40693 AN: 41564

American (AMR) AF: 0.907 AC: 13880 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3047 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5162 AN: 5180

South Asian (SAS) AF: 0.953 AC: 4592 AN: 4820

European-Finnish (FIN) AF: 0.859 AC: 9112 AN: 10606

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59710 AN: 68014

Other (OTH) AF: 0.884 AC: 1869 AN: 2114

Alfa AF: 0.885 Hom.: 48538

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

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 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
PhyloP100		-3.0
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: rs6687620; hg19: chr1-67648460;