5-132657117-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435042.1(TH2LCRR):n.94+7062G>A variant causes a intron, non coding transcript 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: TH2LCRR ENST00000435042.1 intron, non_coding_transcript
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.487

Genes affected

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13	NM_001354992.2	c.-220C>T		5_prime_UTR_variant	2/6
IL13	NM_001354993.2	c.-149C>T		5_prime_UTR_variant	2/5
IL13	NM_001354991.2	c.-93+487C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TH2LCRR	ENST00000435042.1	n.94+7062G>A		intron_variant, non_coding_transcript_variant		5
IL13	ENST00000468334.5	n.420C>T		non_coding_transcript_exon_variant	2/5	3
IL13	ENST00000487267.5	n.147C>T		non_coding_transcript_exon_variant	2/6	3
IL13	ENST00000459878.5	n.107+487C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.191

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

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.231

Alfa AF: 0.170 Hom.: 417

Bravo AF: 0.264

Asia WGS AF: 0.203 AC: 708 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Inherited susceptibility to asthma Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 15, 2005

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.6
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800925; hg19: chr5-131992809;