15-80451009-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014862.4(ARNT2):c.146+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,608,010 control chromosomes in the GnomAD database, including 2,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (154 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1921 hom.)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.71

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-80451009-C-T is Benign according to our data. Variant chr15-80451009-C-T is described in ClinVar as [Benign]. Clinvar id is 1165309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT2	NM_014862.4	c.146+15C>T		intron_variant		ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9	c.146+15C>T		intron_variant		1	NM_014862.4	P1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5266 AN: 152222 Hom.: 155 Cov.: 33

Gnomad AFR AF: 0.00774

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0401

GnomAD3 exomes AF: 0.0517 AC: 12875 AN: 249066 Hom.: 534 AF XY: 0.0515 AC XY: 6950 AN XY: 134866

Gnomad AFR exome AF: 0.00632

Gnomad AMR exome AF: 0.0531

Gnomad ASJ exome AF: 0.0715

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.0678

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.0395

Gnomad OTH exome AF: 0.0505

GnomAD4 exome AF: 0.0430 AC: 62629 AN: 1455670 Hom.: 1921 Cov.: 30 AF XY: 0.0436 AC XY: 31593 AN XY: 724178

Gnomad4 AFR exome AF: 0.00627

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.0661

Gnomad4 FIN exome AF: 0.0155

Gnomad4 NFE exome AF: 0.0376

Gnomad4 OTH exome AF: 0.0496

GnomAD4 genome AF: 0.0346 AC: 5264 AN: 152340 Hom.: 154 Cov.: 33 AF XY: 0.0348 AC XY: 2592 AN XY: 74486

Gnomad4 AFR AF: 0.00769

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0392

Alfa AF: 0.0394 Hom.: 29

Bravo AF: 0.0371

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.14
Dann	Benign	0.78

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: rs2278708; hg19: chr15-80743350; COSMIC: COSV57585611;