rs1891385

Positions:

• chr9-6219845-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):​c.-12+3993A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,208 control chromosomes in the GnomAD database, including 1,178 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 0.11 (1178 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.-12+3993A>C		intron_variant		ENST00000682010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.-12+3993A>C		intron_variant			NM_033439.4	P1
IL33	ENST00000417746.6	c.-12+3993A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16290 AN: 152090 Hom.: 1179 Cov.: 31

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.107 AC: 16283 AN: 152208 Hom.: 1178 Cov.: 31 AF XY: 0.113 AC XY: 8388 AN XY: 74406

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.116

Alfa AF: 0.116 Hom.: 1432

Bravo AF: 0.103

Asia WGS AF: 0.167 AC: 579 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1891385; hg19: chr9-6219845;