rs1891385

Variant names:

• chr9-6219845-A-C
• rs1891385
• NM_033439.4:c.-12+3993A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.-12+3993A>C		intron	N/A	NP_254274.1	O95760-1
	IL33	NM_001314044.2		c.-12+4643A>C		intron	N/A	NP_001300973.1	O95760-1
	IL33	NM_001314046.2		c.-12+3993A>C		intron	N/A	NP_001300975.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.-12+3993A>C		intron	N/A	ENSP00000507310.1	O95760-1
	IL33	ENST00000893939.1		c.-12+4643A>C		intron	N/A	ENSP00000563998.1
	IL33	ENST00000893940.1		c.-12+4670A>C		intron	N/A	ENSP00000563999.1

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

African (AFR) AF: 0.0250 AC: 1038 AN: 41566

American (AMR) AF: 0.178 AC: 2716 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1304 AN: 5164

South Asian (SAS) AF: 0.156 AC: 751 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1753 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7932 AN: 68008

Other (OTH) AF: 0.116 AC: 245 AN: 2110

Alfa AF: 0.109 Hom.: 1720

Bravo AF: 0.103

Asia WGS AF: 0.167 AC: 579 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.70
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1891385; hg19: chr9-6219845;