15-80470185-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014862.4(ARNT2):c.195-28del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.79 (47425 hom., cov: 0)
  • Exomes 𝑓: 0.77 (426178 hom.)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400

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 -10 ACMG points.

• BP6: Variant 15-80470185-TC-T is Benign according to our data. Variant chr15-80470185-TC-T is described in ClinVar as [Benign]. Clinvar id is 1192449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT2	NM_014862.4	c.195-28del		intron_variant		ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9	c.195-28del		intron_variant		1	NM_014862.4	P1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119741 AN: 151926 Hom.: 47384 Cov.: 0

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.783

GnomAD3 exomes AF: 0.778 AC: 180696 AN: 232372 Hom.: 70708 AF XY: 0.774 AC XY: 96722 AN XY: 125010

Gnomad AFR exome AF: 0.828

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.948

Gnomad SAS exome AF: 0.722

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.769

Gnomad OTH exome AF: 0.768

GnomAD4 exome AF: 0.769 AC: 1103885 AN: 1434822 Hom.: 426178 Cov.: 0 AF XY: 0.768 AC XY: 547793 AN XY: 713242

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.954

Gnomad4 SAS exome AF: 0.717

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.779

GnomAD4 genome AF: 0.788 AC: 119834 AN: 152044 Hom.: 47425 Cov.: 0 AF XY: 0.789 AC XY: 58659 AN XY: 74304

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.786

Alfa AF: 0.763 Hom.: 4262

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Webb-Dattani syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs5814026; hg19: chr15-80762526;