rs1048274

Variant names:

• chr9-6256292-G-A
• rs1048274
• NM_033439.4:c.*124G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-6256292-G-A
• chr9-6256292-G-C
• chr9-6256292-G-T

Variant summary

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

The NM_033439.4(IL33):​c.*124G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 656,900 control chromosomes in the GnomAD database, including 39,517 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 (9892 hom., cov: 32)
  • Exomes 𝑓: 0.34 (29625 hom.)
• Consequence: IL33 NM_033439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 27 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=-0.72).
• 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.*124G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.*124G>A		3_prime_UTR_variant	Exon 8 of 8		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53687 AN: 151828 Hom.: 9876 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.336 AC: 169915 AN: 504954 Hom.: 29625 Cov.: 6 AF XY: 0.337 AC XY: 89545 AN XY: 265502

African (AFR) AF: 0.384 AC: 5114 AN: 13332

American (AMR) AF: 0.514 AC: 9842 AN: 19158

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 3846 AN: 14354

East Asian (EAS) AF: 0.462 AC: 14661 AN: 31768

South Asian (SAS) AF: 0.386 AC: 16829 AN: 43548

European-Finnish (FIN) AF: 0.354 AC: 12824 AN: 36206

Middle Eastern (MID) AF: 0.415 AC: 860 AN: 2072

European-Non Finnish (NFE) AF: 0.305 AC: 96587 AN: 316852

Other (OTH) AF: 0.338 AC: 9352 AN: 27664

GnomAD4 genome AF: 0.354 AC: 53726 AN: 151946 Hom.: 9892 Cov.: 32 AF XY: 0.360 AC XY: 26726 AN XY: 74304

African (AFR) AF: 0.379 AC: 15700 AN: 41418

American (AMR) AF: 0.462 AC: 7043 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3464

East Asian (EAS) AF: 0.470 AC: 2434 AN: 5176

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3607 AN: 10556

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20994 AN: 67936

Other (OTH) AF: 0.348 AC: 736 AN: 2112

Alfa AF: 0.326 Hom.: 24079

Bravo AF: 0.364

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		0.18
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: rs1048274; hg19: chr9-6256292; COSMIC: COSV67343594; COSMIC: COSV67343594;