rs2069739

Positions:

• chr5-132656916-A-G

Variant summary

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

The ENST00000435042.1(TH2LCRR):​n.94+7263T>C 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 0.0936 in 152,512 control chromosomes in the GnomAD database, including 1,738 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 0.094 (1737 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1 hom.)
• Consequence: TH2LCRR ENST00000435042.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_001354991.2	c.-93+286A>G		intron_variant			NP_001341920.1
IL13	NM_001354992.2	c.-271-150A>G		intron_variant			NP_001341921.1
IL13	NM_001354993.2	c.-200-150A>G		intron_variant			NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TH2LCRR	ENST00000435042.1	n.94+7263T>C		intron_variant, non_coding_transcript_variant		5
IL13	ENST00000459878.5	n.107+286A>G		intron_variant, non_coding_transcript_variant		3
IL13	ENST00000468334.5	n.369-150A>G		intron_variant, non_coding_transcript_variant		3
IL13	ENST00000487267.5	n.96-150A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14216 AN: 152054 Hom.: 1733 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0409

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0353 AC: 12 AN: 340 Hom.: 1 AF XY: 0.0313 AC XY: 7 AN XY: 224

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.0937 AC: 14261 AN: 152172 Hom.: 1737 Cov.: 32 AF XY: 0.0916 AC XY: 6815 AN XY: 74428

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0412

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0732

Alfa AF: 0.0667 Hom.: 249

Bravo AF: 0.106

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2069739; hg19: chr5-131992608;