rs8041826

Variant names:

• chr15-80410644-A-G
• rs8041826
• NM_014862.4:c.31+6098A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014862.4(ARNT2):​c.31+6098A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,044 control chromosomes in the GnomAD database, including 6,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.26 (6807 hom., cov: 32)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.179
• Publications: 10 publications found

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-DT (HGNC:56077): (ARNT2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.31+6098A>G		intron_variant	Intron 1 of 18	ENST00000303329.9	NP_055677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9	c.31+6098A>G		intron_variant	Intron 1 of 18	1	NM_014862.4	ENSP00000307479.4
ARNT2	ENST00000529181.1	n.197+6098A>G		intron_variant	Intron 1 of 4	1
ARNT2-DT	ENST00000794190.1	n.114+1145T>C		intron_variant	Intron 1 of 5
ARNT2-DT	ENST00000794218.1	n.142+1145T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39540 AN: 151926 Hom.: 6790 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.260 AC: 39604 AN: 152044 Hom.: 6807 Cov.: 32 AF XY: 0.255 AC XY: 18964 AN XY: 74322

African (AFR) AF: 0.493 AC: 20419 AN: 41430

American (AMR) AF: 0.203 AC: 3099 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.175 AC: 906 AN: 5174

South Asian (SAS) AF: 0.0876 AC: 421 AN: 4806

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11544 AN: 67986

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.191 Hom.: 14909

Bravo AF: 0.268

Asia WGS AF: 0.155 AC: 538 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

May 13, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8041826; hg19: chr15-80702986;