5-132660977-T-C

Variant names:

• chr5-132660977-T-C
• rs847
• NM_002188.3:c.*695T>C

Variant summary

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

The NM_002188.3(IL13):​c.*695T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,610 control chromosomes in the GnomAD database, including 47,641 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 0.79 (47526 hom., cov: 32)
  • Exomes 𝑓: 0.68 (115 hom.)
• Consequence: IL13 NM_002188.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 47 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 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.*695T>C		3_prime_UTR	Exon 4 of 4	NP_002179.2
	IL13	NM_001354991.2		c.*695T>C		3_prime_UTR	Exon 5 of 5	NP_001341920.1
	IL13	NM_001354992.2		c.*695T>C		3_prime_UTR	Exon 6 of 6	NP_001341921.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	ENST00000304506.7	TSL:1 MANE Select	c.*695T>C		3_prime_UTR	Exon 4 of 4	ENSP00000304915.3
	TH2LCRR	ENST00000435042.1	TSL:5	n.94+3202A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119321 AN: 151994 Hom.: 47486 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.681 AC: 339 AN: 498 Hom.: 115 Cov.: 0 AF XY: 0.677 AC XY: 203 AN XY: 300

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.840 AC: 89 AN: 106

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.630 AC: 233 AN: 370

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.857 AC: 12 AN: 14

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.785 AC: 119418 AN: 152112 Hom.: 47526 Cov.: 32 AF XY: 0.774 AC XY: 57545 AN XY: 74336

African (AFR) AF: 0.873 AC: 36256 AN: 41538

American (AMR) AF: 0.668 AC: 10200 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2596 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3481 AN: 5160

South Asian (SAS) AF: 0.710 AC: 3421 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6482 AN: 10528

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54278 AN: 67998

Other (OTH) AF: 0.792 AC: 1674 AN: 2114

Alfa AF: 0.786 Hom.: 21012

Bravo AF: 0.792

Asia WGS AF: 0.696 AC: 2422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.41
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: rs847; hg19: chr5-131996669;