chr9-6253710-G-C

Position:

• chr9-6253710-G-C

Variant summary

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

The NM_033439.4(IL33):​c.520+108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 758,366 control chromosomes in the GnomAD database, including 41,394 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 0.35 (9849 hom., cov: 32)
  • Exomes 𝑓: 0.31 (31545 hom.)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

Genes affected

IL33 (HGNC:16028): (interleukin 33) The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

LOC107987046 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.520+108G>C		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-25415C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.520+108G>C		intron_variant			NM_033439.4	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53554 AN: 151868 Hom.: 9832 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.314 AC: 190530 AN: 606380 Hom.: 31545 AF XY: 0.316 AC XY: 99618 AN XY: 315474

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.353 AC: 53595 AN: 151986 Hom.: 9849 Cov.: 32 AF XY: 0.359 AC XY: 26652 AN XY: 74282

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.349

Alfa AF: 0.202 Hom.: 434

Bravo AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10975520; hg19: chr9-6253710; COSMIC: COSV67343581;