rs1139651

Positions:

• chr15-80597665-G-A

Variant summary

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

The NM_014862.4(ARNT2):​c.*3967G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 157,822 control chromosomes in the GnomAD database, including 1,921 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 0.14 (1861 hom., cov: 32)
  • Exomes 𝑓: 0.11 (60 hom.)
• Consequence: ARNT2 NM_014862.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

Genes affected

ARNT2 (HGNC:16876): (aryl hydrocarbon receptor nuclear translocator 2) This gene encodes a member of the basic-helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily of transcription factors. The encoded protein acts as a partner for several sensor proteins of the bHLH-PAS family, forming heterodimers with the sensor proteins that bind regulatory DNA sequences in genes responsive to developmental and environmental stimuli. Under hypoxic conditions, the encoded protein complexes with hypoxia-inducible factor 1alpha in the nucleus and this complex binds to hypoxia-responsive elements in enhancers and promoters of oxygen-responsive genes. A highly similar protein in mouse forms functional complexes with both aryl hydrocarbon receptors and Single-minded proteins, suggesting additional roles for the encoded protein in the metabolism of xenobiotic compounds and the regulation of neurogenesis, respectively. [provided by RefSeq, Dec 2013]

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 = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.*3967G>A		3_prime_UTR_variant	19/19	ENST00000303329.9	NP_055677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9	c.*3967G>A		3_prime_UTR_variant	19/19	1	NM_014862.4	ENSP00000307479	P1
ARNT2	ENST00000533983.5	c.*3967G>A		3_prime_UTR_variant	20/20	5		ENSP00000453651

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20973 AN: 152054 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.112 AC: 632 AN: 5650 Hom.: 60 Cov.: 0 AF XY: 0.114 AC XY: 337 AN XY: 2962

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0946

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0810

Gnomad4 NFE exome AF: 0.0794

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.138 AC: 21015 AN: 152172 Hom.: 1861 Cov.: 32 AF XY: 0.140 AC XY: 10400 AN XY: 74386

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0912 Hom.: 1375

Bravo AF: 0.147

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.012
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1139651; hg19: chr15-80890006;