1-67149804-T-C

Variant names:

• chr1-67149804-T-C
• rs10889657
• ENST00000637002.1:n.-30+10643T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637002.1(IL23R):​n.-30+10643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,048 control chromosomes in the GnomAD database, including 6,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6469 hom., cov: 32)
• Consequence: IL23R ENST00000637002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	XM_011540790.4	c.-30+10643T>C		intron_variant	Intron 1 of 10		XP_011539092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000637002.1	n.-30+10643T>C		intron_variant	Intron 1 of 10	1		ENSP00000490340.2
C1orf141	ENST00000371007.6	c.-103-18577A>G		intron_variant	Intron 1 of 7	5		ENSP00000360046.1
C1orf141	ENST00000448166.6	c.-103-18577A>G		intron_variant	Intron 1 of 9	5		ENSP00000415519.2
IL23R	ENST00000697222.1	c.-30+10643T>C		intron_variant	Intron 1 of 2			ENSP00000513189.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42741 AN: 151930 Hom.: 6457 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42785 AN: 152048 Hom.: 6469 Cov.: 32 AF XY: 0.284 AC XY: 21104 AN XY: 74318

African (AFR) AF: 0.182 AC: 7556 AN: 41494

American (AMR) AF: 0.409 AC: 6252 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1584 AN: 5182

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4808

European-Finnish (FIN) AF: 0.327 AC: 3442 AN: 10536

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21019 AN: 67976

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

Alfa AF: 0.285 Hom.: 5362

Bravo AF: 0.286

Asia WGS AF: 0.347 AC: 1206 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.47
PhyloP100		0.28
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: rs10889657; hg19: chr1-67615487;