Genetic Variant NM_144701.3:c.956-8194A>G (chr1-67228519-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144701.3(IL23R):c.956-8194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,464 control chromosomes in the GnomAD database, including 7,312 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 0.29 ( 7312 hom., cov: 29)

Consequence

IL23R
NM_144701.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

Publications

192 publications found

Variant links:

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]

IL23R links:

C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

C1orf141 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_144701.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.956-8194A>G		intron	N/A	NP_653302.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL23R	ENST00000347310.10	TSL:1 MANE Select	c.956-8194A>G	intron	N/A	ENSP00000321345.5	Q5VWK5-1
IL23R	ENST00000425614.3	TSL:1	c.191-8194A>G	intron	N/A	ENSP00000387640.2	Q5VWK5-6
IL23R	ENST00000473881.2	TSL:1	n.190+8789A>G	intron	N/A	ENSP00000486667.1	A0A0D9SFJ7

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43206

AN:

151346

Hom.:

7304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.308

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

GnomAD4 genome

AF:

0.285

AC:

43236

AN:

151464

Hom.:

7312

Cov.:

AF XY:

0.292

AC XY:

21573

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.164

AC:

6760

AN:

41308

American (AMR)

AF:

0.266

AC:

4047

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1171

AN:

3464

East Asian (EAS)

AF:

0.724

AC:

3722

AN:

5138

South Asian (SAS)

AF:

0.587

AC:

2797

AN:

4768

European-Finnish (FIN)

AF:

0.294

AC:

3070

AN:

10454

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20602

AN:

67830

Other (OTH)

AF:

0.311

AC:

654

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1352

2705

4057

5410

6762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.308

Hom.:

32794

Bravo

AF:

0.275

Asia WGS

AF:

0.579

AC:

2007

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.7

(source)

DANN

Benign

0.78

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over