rs848

Variant names:

• chr5-132660808-A-C
• rs848
• NM_002188.3:c.*526A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132660808-A-C
• chr5-132660808-A-G
• chr5-132660808-A-T

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_002188.3(IL13):c.*526A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.68 (AC=108,015) in the gnomAD database across 158,878 control chromosomes, including 38,217 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.797. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (36320 hom., cov: 31)
  • Exomes 𝑓: 0.72 (1897 hom.)
• Consequence: IL13 NM_002188.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 137 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)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7972 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002188.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	NM_002188.3	MANE Select	c.*526A>C		3_prime_UTR	Exon 4 of 4	NP_002179.2
	IL13	NM_001354991.2		c.*526A>C		3_prime_UTR	Exon 5 of 5	NP_001341920.1	Q4VB53
	IL13	NM_001354992.2		c.*526A>C		3_prime_UTR	Exon 6 of 6	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.*526A>C		3_prime_UTR	Exon 4 of 4	ENSP00000304915.3	P35225
	TH2LCRR	ENST00000435042.1	TSL:5	n.94+3371T>G		intron	N/A
	IL13	ENST00000459878.5	TSL:3	n.*194A>C		downstream_gene	N/A

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.678	AC:102993	Hom:36321	AN:151830	Cov:31
GnomAD4 exome	AF: 0.721	AC:4995	Hom:1897	AN:6932	Cov:0
GnomAD4 genome	AF: 0.678	AC:103020	Hom:36320	AN:151946	Cov:31
TOPMed (Bravo)	AF: 0.669	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.757	AC:153458	Hom:59156	AN:202784	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.724	AC:1695	Hom:621	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.684	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.800	AC:240	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.665	AC:2315	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.681	AC:4927	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.818	AC:144	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.691	AC:84741	Hom:29255	AN:122710	Cov:
Turkish Variome	AF: 0.763	AC:1176	Hom:448	AN:1542	Cov:
UK10K	AF: 0.813	AC:6145	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.682	AC:6108	Hom:2097	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.257	5934	23106	0.125	3705	29590

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.14
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.75
GPN-Star LLR	N/A	-2.0
GPN-Star score	N/A	2.0
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-1.2

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs848;

hg19: chr5-131996500;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar