rs12593988

Positions:

• chr15-80413485-A-G

Variant summary

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

The NM_014862.4(ARNT2):​c.31+8939A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,232 control chromosomes in the GnomAD database, including 50,782 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 0.81 (50782 hom., cov: 33)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT2	NM_014862.4	c.31+8939A>G		intron_variant		ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9	c.31+8939A>G		intron_variant		1	NM_014862.4	P1
ARNT2	ENST00000529181.1	n.197+8939A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123935 AN: 152114 Hom.: 50746 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.815 AC: 124029 AN: 152232 Hom.: 50782 Cov.: 33 AF XY: 0.820 AC XY: 61001 AN XY: 74436

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.820

Alfa AF: 0.805 Hom.: 53595

Bravo AF: 0.813

Asia WGS AF: 0.928 AC: 3226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.080
DANN	Benign	0.46

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: rs12593988; hg19: chr15-80705827;