15-80441756-C-T

Variant summary

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

The NM_014862.4(ARNT2):c.32-9124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,112 control chromosomes in the GnomAD database, including 9,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.32 (9236 hom., cov: 33)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.165

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT2	NM_014862.4	c.32-9124C>T		intron_variant		ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9	c.32-9124C>T		intron_variant		1	NM_014862.4	P1
	ENST00000666336.1	n.996G>A		non_coding_transcript_exon_variant	1/2
	ENST00000548231.1	n.866+2531G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48978 AN: 151994 Hom.: 9232 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 49004 AN: 152112 Hom.: 9236 Cov.: 33 AF XY: 0.330 AC XY: 24528 AN XY: 74354

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.325

Alfa AF: 0.369 Hom.: 21867

Bravo AF: 0.317

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 12, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.5
Dann	Benign	0.51

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: rs3901896; hg19: chr15-80734097;