1-67149804-T-C

Position:

• chr1-67149804-T-C

Variant summary

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

The ENST00000637002.1(IL23R):​c.-30+10643T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-0.9).
• 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/exons	MANE	UniProt
IL23R	XM_011540790.4	c.-30+10643T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL23R	ENST00000637002.1	c.-30+10643T>C		intron_variant, NMD_transcript_variant		1
C1orf141	ENST00000371007.6	c.-103-18577A>G		intron_variant		5		P1
C1orf141	ENST00000448166.6	c.-103-18577A>G		intron_variant		5
IL23R	ENST00000697222.1	c.-30+10643T>C		intron_variant

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

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.302

Alfa AF: 0.284 Hom.: 4528

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

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: rs10889657; hg19: chr1-67615487;