Variant chr15-80451009-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.71

Variant links:

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]

ARNT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	c.146+15C>T		intron_variant		ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9 linkuse as main transcript	c.146+15C>T		intron_variant		1	NM_014862.4	P1	Q9HBZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5266

AN:

152222

Hom.:

155

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0436

AC XY:

31593

AN XY:

724178

show subpopulations

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.:

AF XY:

0.0348

AC XY:

2592

AN XY:

74486

show subpopulations

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.:

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over