chr15-80597760-T-C

Position:

• chr15-80597760-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.*4062T>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 0.397 in 155,572 control chromosomes in the GnomAD database, including 15,052 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 0.40 (14891 hom., cov: 33)
  • Exomes 𝑓: 0.29 (161 hom.)
• Consequence: ARNT2 NM_014862.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.*4062T>C		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.*4062T>C		3_prime_UTR_variant	19/19	1	NM_014862.4	ENSP00000307479.4
ARNT2	ENST00000533983.5	c.*4062T>C		3_prime_UTR_variant	20/20	5		ENSP00000453651.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60641 AN: 152092 Hom.: 14847 Cov.: 33

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.293 AC: 985 AN: 3362 Hom.: 161 Cov.: 0 AF XY: 0.287 AC XY: 500 AN XY: 1744

Gnomad4 AFR exome AF: 0.636

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.399 AC: 60750 AN: 152210 Hom.: 14891 Cov.: 33 AF XY: 0.396 AC XY: 29485 AN XY: 74424

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.351

Alfa AF: 0.307 Hom.: 10673

Bravo AF: 0.420

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.70

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: rs7484; hg19: chr15-80890101; COSMIC: COSV57592239; COSMIC: COSV57592239;