9-6257898-A-G

Position:

• chr9-6257898-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.*1730A>G		3_prime_UTR_variant	8/8	ENST00000682010.1	NP_254274.1
LOC107987046	XR_001746614.2	n.153-29603T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.*1730A>G		3_prime_UTR_variant	8/8		NM_033439.4	ENSP00000507310	P1
IL33	ENST00000381434.7	c.*1730A>G		3_prime_UTR_variant	7/7	1		ENSP00000370842	P1
IL33	ENST00000417746.6	c.*1730A>G		3_prime_UTR_variant	5/5	2		ENSP00000394039
IL33	ENST00000456383.3	c.*1730A>G		3_prime_UTR_variant	6/6	5		ENSP00000414238

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

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

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.819

Alfa AF: 0.873 Hom.: 24580

Bravo AF: 0.781

Asia WGS AF: 0.945 AC: 3273 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs8172; hg19: chr9-6257898;