9-6257898-A-G

Variant names:

• chr9-6257898-A-G
• rs8172
• NM_033439.4:c.*1730A>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.*1730A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,140 control chromosomes in the GnomAD database, including 51,742 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 0.80 (51742 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: IL33 NM_033439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	NM_033439.4	MANE Select	c.*1730A>G		3_prime_UTR	Exon 8 of 8	NP_254274.1	O95760-1
	IL33	NM_001314044.2		c.*1730A>G		3_prime_UTR	Exon 8 of 8	NP_001300973.1	O95760-1
	IL33	NM_001314045.2		c.*1730A>G		3_prime_UTR	Exon 8 of 8	NP_001300974.1	O95760-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.*1730A>G		3_prime_UTR	Exon 8 of 8	ENSP00000507310.1	O95760-1
	IL33	ENST00000381434.7	TSL:1	c.*1730A>G		3_prime_UTR	Exon 7 of 7	ENSP00000370842.3	O95760-1
	IL33	ENST00000893939.1		c.*1730A>G		3_prime_UTR	Exon 8 of 8	ENSP00000563998.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121563 AN: 152022 Hom.: 51738 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.817

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.799 AC: 121583 AN: 152140 Hom.: 51742 Cov.: 33 AF XY: 0.807 AC XY: 60036 AN XY: 74398

African (AFR) AF: 0.477 AC: 19771 AN: 41452

American (AMR) AF: 0.882 AC: 13483 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3171 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5186

South Asian (SAS) AF: 0.964 AC: 4650 AN: 4824

European-Finnish (FIN) AF: 0.951 AC: 10080 AN: 10598

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62432 AN: 68002

Other (OTH) AF: 0.819 AC: 1731 AN: 2114

Alfa AF: 0.868 Hom.: 28755

Bravo AF: 0.781

Asia WGS AF: 0.945 AC: 3273 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.41
PhyloP100		2.2
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: rs8172; hg19: chr9-6257898;