9-6253710-G-C

Variant names:

• chr9-6253710-G-C
• rs10975520
• NM_033439.4:c.520+108G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ENSG00000294323 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.520+108G>C		intron_variant	Intron 6 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.520+108G>C		intron_variant	Intron 6 of 7		NM_033439.4	ENSP00000507310.1

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

African (AFR) AF: 0.365 AC: 5650 AN: 15472

American (AMR) AF: 0.508 AC: 11363 AN: 22380

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 3958 AN: 15774

East Asian (EAS) AF: 0.458 AC: 14910 AN: 32540

South Asian (SAS) AF: 0.366 AC: 17089 AN: 46696

European-Finnish (FIN) AF: 0.350 AC: 15384 AN: 43940

Middle Eastern (MID) AF: 0.385 AC: 1222 AN: 3170

European-Non Finnish (NFE) AF: 0.281 AC: 111347 AN: 396046

Other (OTH) AF: 0.316 AC: 9607 AN: 30362

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

African (AFR) AF: 0.375 AC: 15551 AN: 41454

American (AMR) AF: 0.462 AC: 7045 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2428 AN: 5158

South Asian (SAS) AF: 0.402 AC: 1934 AN: 4816

European-Finnish (FIN) AF: 0.343 AC: 3617 AN: 10560

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21021 AN: 67954

Other (OTH) AF: 0.349 AC: 735 AN: 2108

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10975520; hg19: chr9-6253710; COSMIC: COSV67343581;