chr9-6242950-C-T

Position:

• chr9-6242950-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033439.4(IL33):​c.91+1165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,928 control chromosomes in the GnomAD database, including 28,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.59 (28409 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 9-6242950-C-T is Benign according to our data. Variant chr9-6242950-C-T is described in ClinVar as [Benign]. Clinvar id is 1288261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.91+1165C>T		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-14655G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.91+1165C>T		intron_variant			NM_033439.4	P1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89977 AN: 151810 Hom.: 28399 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.592 AC: 90006 AN: 151928 Hom.: 28409 Cov.: 31 AF XY: 0.600 AC XY: 44521 AN XY: 74254

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.636

Alfa AF: 0.671 Hom.: 30952

Bravo AF: 0.585

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 30544846) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.15

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: rs4742170; hg19: chr9-6242950;