5-132657117-C-T

Variant names:

• chr5-132657117-C-T
• rs1800925
• NM_001354992.2:c.-220C>T

Variant summary

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

The NM_001354992.2(IL13):​c.-220C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 155,818 control chromosomes in the GnomAD database, including 5,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5693 hom., cov: 32)
  • Exomes 𝑓: 0.19 (61 hom.)
• Consequence: IL13 NM_001354992.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.487
• Publications: 363 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354992.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	NM_001354992.2		c.-220C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001341921.1
	IL13	NM_001354993.2		c.-149C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001341922.1
	IL13	NM_001354992.2		c.-220C>T		5_prime_UTR	Exon 2 of 6	NP_001341921.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	ENST00000468334.5	TSL:3	n.420C>T		non_coding_transcript_exon	Exon 2 of 5
	IL13	ENST00000487267.5	TSL:3	n.147C>T		non_coding_transcript_exon	Exon 2 of 6
	TH2LCRR	ENST00000435042.1	TSL:5	n.94+7062G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39202 AN: 151940 Hom.: 5672 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.188 AC: 706 AN: 3760 Hom.: 61 Cov.: 0 AF XY: 0.187 AC XY: 376 AN XY: 2012

African (AFR) AF: 0.375 AC: 30 AN: 80

American (AMR) AF: 0.179 AC: 10 AN: 56

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 19 AN: 90

East Asian (EAS) AF: 0.174 AC: 80 AN: 460

South Asian (SAS) AF: 0.300 AC: 9 AN: 30

European-Finnish (FIN) AF: 0.181 AC: 67 AN: 370

Middle Eastern (MID) AF: 0.154 AC: 4 AN: 26

European-Non Finnish (NFE) AF: 0.183 AC: 445 AN: 2428

Other (OTH) AF: 0.191 AC: 42 AN: 220

GnomAD4 genome AF: 0.258 AC: 39261 AN: 152058 Hom.: 5693 Cov.: 32 AF XY: 0.258 AC XY: 19149 AN XY: 74328

African (AFR) AF: 0.394 AC: 16320 AN: 41440

American (AMR) AF: 0.221 AC: 3382 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3466

East Asian (EAS) AF: 0.170 AC: 877 AN: 5170

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4822

European-Finnish (FIN) AF: 0.207 AC: 2188 AN: 10572

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13995 AN: 67982

Other (OTH) AF: 0.231 AC: 487 AN: 2108

Alfa AF: 0.225 Hom.: 6169

Bravo AF: 0.264

Asia WGS AF: 0.203 AC: 708 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Inherited susceptibility to asthma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.42
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs1800925; hg19: chr5-131992809;