5-132658339-C-A

Variant names:

• chr5-132658339-C-A
• rs34255686
• NM_002188.3:c.153C>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002188.3(IL13):​c.153C>A​(p.Val51Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,609,610 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (44 hom.)
• Consequence: IL13 NM_002188.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-132658339-C-A is Benign according to our data. Variant chr5-132658339-C-A is described in ClinVar as [Benign]. Clinvar id is 785136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.095 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0136 (2068/152332) while in subpopulation AFR AF = 0.0474 (1972/41576). AF 95% confidence interval is 0.0457. There are 44 homozygotes in GnomAd4. There are 975 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13	NM_002188.3	c.153C>A	p.Val51Val	synonymous_variant	Exon 1 of 4	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.-43C>A		5_prime_UTR_variant	Exon 2 of 5		NP_001341920.1
IL13	NM_001354992.2	c.-43C>A		5_prime_UTR_variant	Exon 3 of 6		NP_001341921.1
IL13	NM_001354993.2	c.-21-1079C>A		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.153C>A	p.Val51Val	synonymous_variant	Exon 1 of 4	1	NM_002188.3	ENSP00000304915.3

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2065 AN: 152214 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00349 AC: 870 AN: 248968 AF XY: 0.00250

Gnomad AFR exome AF: 0.0477

Gnomad AMR exome AF: 0.00242

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00132 AC: 1924 AN: 1457278 Hom.: 44 Cov.: 28 AF XY: 0.00111 AC XY: 805 AN XY: 725152

African (AFR) AF: 0.0460 AC: 1534 AN: 33328

American (AMR) AF: 0.00285 AC: 127 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5750

European-Non Finnish (NFE) AF: 0.0000586 AC: 65 AN: 1108546

Other (OTH) AF: 0.00301 AC: 181 AN: 60212

GnomAD4 genome AF: 0.0136 AC: 2068 AN: 152332 Hom.: 44 Cov.: 32 AF XY: 0.0131 AC XY: 975 AN XY: 74486

African (AFR) AF: 0.0474 AC: 1972 AN: 41576

American (AMR) AF: 0.00444 AC: 68 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00544 Hom.: 48

Bravo AF: 0.0157

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		-0.095
PromoterAI		-0.054	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34255686; hg19: chr5-131994031;