1-67207429-A-G

Variant names:

• chr1-67207429-A-G
• rs4655691
• NM_144701.3:c.798+374A>G

Variant summary

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

The NM_144701.3(IL23R):​c.798+374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 151,912 control chromosomes in the GnomAD database, including 47,559 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 0.79 (47559 hom., cov: 30)
• Consequence: IL23R NM_144701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	NM_144701.3	MANE Select	c.798+374A>G		intron	N/A	NP_653302.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23R	ENST00000347310.10	TSL:1 MANE Select	c.798+374A>G		intron	N/A	ENSP00000321345.5
	IL23R	ENST00000637002.1	TSL:1	n.*259+374A>G		intron	N/A	ENSP00000490340.2
	IL23R	ENST00000697164.1		c.798+374A>G		intron	N/A	ENSP00000513153.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119538 AN: 151794 Hom.: 47510 Cov.: 30

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.788 AC: 119642 AN: 151912 Hom.: 47559 Cov.: 30 AF XY: 0.787 AC XY: 58390 AN XY: 74200

African (AFR) AF: 0.875 AC: 36268 AN: 41452

American (AMR) AF: 0.782 AC: 11953 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2345 AN: 3472

East Asian (EAS) AF: 0.969 AC: 5013 AN: 5172

South Asian (SAS) AF: 0.861 AC: 4130 AN: 4796

European-Finnish (FIN) AF: 0.700 AC: 7357 AN: 10512

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50072 AN: 67918

Other (OTH) AF: 0.758 AC: 1598 AN: 2108

Alfa AF: 0.756 Hom.: 5430

Bravo AF: 0.796

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		-1.6
PromoterAI		0.011	Neutral
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: rs4655691; hg19: chr1-67673112;