9-6255152-A-G

Variant names:

• chr9-6255152-A-G
• rs1412420
• NM_033439.4:c.612+599A>G

Variant summary

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

The NM_033439.4(IL33):​c.612+599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 152,154 control chromosomes in the GnomAD database, including 68,007 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 0.95 (68007 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 8 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 = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.612+599A>G		intron_variant	Intron 7 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.612+599A>G		intron_variant	Intron 7 of 7		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143690 AN: 152036 Hom.: 67958 Cov.: 31

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.945 AC: 143798 AN: 152154 Hom.: 68007 Cov.: 31 AF XY: 0.947 AC XY: 70480 AN XY: 74396

African (AFR) AF: 0.915 AC: 37964 AN: 41504

American (AMR) AF: 0.957 AC: 14588 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3322 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5189 AN: 5192

South Asian (SAS) AF: 0.980 AC: 4715 AN: 4812

European-Finnish (FIN) AF: 0.983 AC: 10428 AN: 10604

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64462 AN: 68006

Other (OTH) AF: 0.940 AC: 1984 AN: 2110

Alfa AF: 0.946 Hom.: 6067

Bravo AF: 0.942

Asia WGS AF: 0.986 AC: 3413 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.86
PhyloP100		0.33
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: rs1412420; hg19: chr9-6255152;