rs4655684

Positions:

• chr1-67146089-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637002.1(IL23R):​c.-30+6928C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,994 control chromosomes in the GnomAD database, including 9,084 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 0.34 (9084 hom., cov: 31)
• Consequence: IL23R ENST00000637002.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL23R	XM_011540790.4	c.-30+6928C>T		intron_variant			XP_011539092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000637002.1	c.-30+6928C>T		intron_variant, NMD_transcript_variant		1		ENSP00000490340
C1orf141	ENST00000371007.6	c.-103-14862G>A		intron_variant		5		ENSP00000360046	P1
C1orf141	ENST00000448166.6	c.-103-14862G>A		intron_variant		5		ENSP00000415519
IL23R	ENST00000697222.1	c.-30+6928C>T		intron_variant				ENSP00000513189

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51863 AN: 151876 Hom.: 9062 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.342 AC: 51928 AN: 151994 Hom.: 9084 Cov.: 31 AF XY: 0.343 AC XY: 25482 AN XY: 74276

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.358

Alfa AF: 0.350 Hom.: 1743

Bravo AF: 0.351

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.77
DANN	Benign	0.12

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: rs4655684; hg19: chr1-67611772;