15-80593850-T-C

Position:

• chr15-80593850-T-C

Variant summary

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

The NM_014862.4(ARNT2):​c.*152T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 666,536 control chromosomes in the GnomAD database, including 128,489 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 0.66 (35558 hom., cov: 30)
  • Exomes 𝑓: 0.58 (92931 hom.)
• Consequence: ARNT2 NM_014862.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT2	NM_014862.4	c.*152T>C		3_prime_UTR_variant	19/19	ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9	c.*152T>C		3_prime_UTR_variant	19/19	1	NM_014862.4	P1
ARNT2	ENST00000527771.5	c.*152T>C		3_prime_UTR_variant	19/19	2
ARNT2	ENST00000533983.5	c.*152T>C		3_prime_UTR_variant	20/20	5

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99724 AN: 151682 Hom.: 35489 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.581 AC: 299210 AN: 514736 Hom.: 92931 Cov.: 6 AF XY: 0.588 AC XY: 157844 AN XY: 268438

Gnomad4 AFR exome AF: 0.918

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.946

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.658 AC: 99858 AN: 151800 Hom.: 35558 Cov.: 30 AF XY: 0.663 AC XY: 49155 AN XY: 74166

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.624

Alfa AF: 0.568 Hom.: 12383

Bravo AF: 0.679

Asia WGS AF: 0.870 AC: 3021 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	0.14
DANN	Benign	0.23

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: rs8033706; hg19: chr15-80886191;