ENST00000462480.1:n.598C>G

Variant names:

• chr5-132658770-C-G
• rs1295687
• ENST00000462480.1:n.598C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462480.1(IL13):​n.598C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 182,062 control chromosomes in the GnomAD database, including 70,450 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 0.87 (58137 hom., cov: 32)
  • Exomes 𝑓: 0.91 (12313 hom.)
• Consequence: IL13 ENST00000462480.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.26
• Publications: 18 publications found

Genes affected

IL13 (HGNC:5973): (interleukin 13) This gene encodes an immunoregulatory cytokine produced primarily by activated Th2 cells. This cytokine is involved in several stages of B-cell maturation and differentiation. It up-regulates CD23 and MHC class II expression, and promotes IgE isotype switching of B cells. This cytokine down-regulates macrophage activity, thereby inhibits the production of pro-inflammatory cytokines and chemokines. This cytokine is found to be critical to the pathogenesis of allergen-induced asthma but operates through mechanisms independent of IgE and eosinophils. This gene, IL3, IL5, IL4, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL4. [provided by RefSeq, Jul 2008]

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13	NM_002188.3	c.174+410C>G		intron_variant	Intron 1 of 3	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.-22+410C>G		intron_variant	Intron 2 of 4		NP_001341920.1
IL13	NM_001354992.2	c.-22+410C>G		intron_variant	Intron 3 of 5		NP_001341921.1
IL13	NM_001354993.2	c.-21-648C>G		intron_variant	Intron 2 of 4		NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7	c.174+410C>G		intron_variant	Intron 1 of 3	1	NM_002188.3	ENSP00000304915.3

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132261 AN: 152104 Hom.: 58110 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.906 AC: 27034 AN: 29840 Hom.: 12313 Cov.: 0 AF XY: 0.910 AC XY: 13848 AN XY: 15214

African (AFR) AF: 0.735 AC: 734 AN: 998

American (AMR) AF: 0.766 AC: 2264 AN: 2954

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 814 AN: 876

East Asian (EAS) AF: 0.874 AC: 1261 AN: 1442

South Asian (SAS) AF: 0.925 AC: 1610 AN: 1740

European-Finnish (FIN) AF: 0.884 AC: 1068 AN: 1208

Middle Eastern (MID) AF: 0.873 AC: 96 AN: 110

European-Non Finnish (NFE) AF: 0.938 AC: 17608 AN: 18768

Other (OTH) AF: 0.905 AC: 1579 AN: 1744

GnomAD4 genome AF: 0.869 AC: 132340 AN: 152222 Hom.: 58137 Cov.: 32 AF XY: 0.866 AC XY: 64456 AN XY: 74444

African (AFR) AF: 0.747 AC: 30994 AN: 41506

American (AMR) AF: 0.822 AC: 12575 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3212 AN: 3470

East Asian (EAS) AF: 0.895 AC: 4633 AN: 5176

South Asian (SAS) AF: 0.919 AC: 4419 AN: 4806

European-Finnish (FIN) AF: 0.879 AC: 9329 AN: 10612

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64104 AN: 68028

Other (OTH) AF: 0.893 AC: 1890 AN: 2116

Alfa AF: 0.894 Hom.: 3000

Bravo AF: 0.855

Asia WGS AF: 0.907 AC: 3155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.42
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1295687; hg19: chr5-131994462;