rs1037124

Positions:

• chr15-80439474-G-A

Variant summary

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

The NM_014862.4(ARNT2):​c.32-11406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,034 control chromosomes in the GnomAD database, including 4,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4899 hom., cov: 33)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.32-11406G>A		intron_variant		ENST00000303329.9	NP_055677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9	c.32-11406G>A		intron_variant		1	NM_014862.4	ENSP00000307479.4
ARNT2	ENST00000529181.1	n.198-11406G>A		intron_variant		1
ENSG00000258010	ENST00000548231.1	n.867-3087C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35374 AN: 151916 Hom.: 4886 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.233 AC: 35424 AN: 152034 Hom.: 4899 Cov.: 33 AF XY: 0.230 AC XY: 17126 AN XY: 74326

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.226

Alfa AF: 0.186 Hom.: 5589

Bravo AF: 0.236

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.031
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: rs1037124; hg19: chr15-80731815;