9-6255152-A-G

Position:

• chr9-6255152-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.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

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=-0.85).
• 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/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.612+599A>G		intron_variant		ENST00000682010.1	NP_254274.1
LOC107987046	XR_001746614.2	n.153-26857T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.612+599A>G		intron_variant			NM_033439.4	ENSP00000507310	P1

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

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.957

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.980

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.940

Alfa AF: 0.948 Hom.: 5757

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

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: rs1412420; hg19: chr9-6255152;