rs1881457

Positions:

• chr5-132656717-A-C

Variant summary

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

The ENST00000435042.1(TH2LCRR):​n.94+7462T>G 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 0.208 in 151,468 control chromosomes in the GnomAD database, including 3,331 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 0.21 (3318 hom., cov: 32)
  • Exomes 𝑓: 0.21 (13 hom.)
• Consequence: TH2LCRR ENST00000435042.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_001354991.2	c.-93+87A>C		intron_variant			NP_001341920.1
IL13	NM_001354992.2	c.-272+87A>C		intron_variant			NP_001341921.1
IL13	NM_001354993.2	c.-201+87A>C		intron_variant			NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TH2LCRR	ENST00000435042.1	n.94+7462T>G		intron_variant, non_coding_transcript_variant		5
IL13	ENST00000459878.5	n.107+87A>C		intron_variant, non_coding_transcript_variant		3
IL13	ENST00000468334.5	n.368+87A>C		intron_variant, non_coding_transcript_variant		3
IL13	ENST00000487267.5	n.95+87A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31368 AN: 150856 Hom.: 3310 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.209 AC: 103 AN: 494 Hom.: 13 AF XY: 0.209 AC XY: 75 AN XY: 358

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.208 AC: 31413 AN: 150974 Hom.: 3318 Cov.: 32 AF XY: 0.209 AC XY: 15450 AN XY: 73836

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.202

Alfa AF: 0.205 Hom.: 2614

Bravo AF: 0.202

Asia WGS AF: 0.222 AC: 774 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1881457; hg19: chr5-131992409;