rs2066960

Variant names:

• chr5-132658743-C-A
• rs2066960
• NM_002188.3:c.174+383C>A

Variant summary

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

The NM_002188.3(IL13):​c.174+383C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 198,214 control chromosomes in the GnomAD database, including 2,633 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 0.16 (2175 hom., cov: 32)
  • Exomes 𝑓: 0.12 (458 hom.)
• Consequence: IL13 NM_002188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 28 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002188.3. 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
	IL13	NM_002188.3	MANE Select	c.174+383C>A		intron	N/A	NP_002179.2
	IL13	NM_001354991.2		c.-22+383C>A		intron	N/A	NP_001341920.1	Q4VB53
	IL13	NM_001354992.2		c.-22+383C>A		intron	N/A	NP_001341921.1	Q4VB53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	ENST00000304506.7	TSL:1 MANE Select	c.174+383C>A		intron	N/A	ENSP00000304915.3	P35225
	IL13	ENST00000462480.1	TSL:1	n.571C>A		non_coding_transcript_exon	Exon 1 of 3
	TH2LCRR	ENST00000435042.1	TSL:5	n.94+5436G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23840 AN: 152080 Hom.: 2169 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.121 AC: 5576 AN: 46016 Hom.: 458 Cov.: 0 AF XY: 0.120 AC XY: 2834 AN XY: 23532

African (AFR) AF: 0.206 AC: 326 AN: 1582

American (AMR) AF: 0.192 AC: 637 AN: 3314

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 158 AN: 1554

East Asian (EAS) AF: 0.292 AC: 690 AN: 2362

South Asian (SAS) AF: 0.108 AC: 248 AN: 2298

European-Finnish (FIN) AF: 0.177 AC: 404 AN: 2288

Middle Eastern (MID) AF: 0.139 AC: 28 AN: 202

European-Non Finnish (NFE) AF: 0.0930 AC: 2759 AN: 29662

Other (OTH) AF: 0.118 AC: 326 AN: 2754

GnomAD4 genome AF: 0.157 AC: 23872 AN: 152198 Hom.: 2175 Cov.: 32 AF XY: 0.162 AC XY: 12088 AN XY: 74418

African (AFR) AF: 0.205 AC: 8492 AN: 41494

American (AMR) AF: 0.182 AC: 2786 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1896 AN: 5168

South Asian (SAS) AF: 0.122 AC: 590 AN: 4818

European-Finnish (FIN) AF: 0.208 AC: 2209 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7151 AN: 68020

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.127 Hom.: 2334

Bravo AF: 0.161

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.051
DANN	Benign	0.27
PhyloP100		-1.2
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: rs2066960; hg19: chr5-131994435;