rs16972160

Positions:

• chr15-80457032-T-C

Variant summary

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

The NM_014862.4(ARNT2):​c.147-897T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,232 control chromosomes in the GnomAD database, including 783 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 0.083 (783 hom., cov: 32)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT2	NM_014862.4	c.147-897T>C		intron_variant		ENST00000303329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT2	ENST00000303329.9	c.147-897T>C		intron_variant		1	NM_014862.4	P1

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12554 AN: 152114 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0826 AC: 12572 AN: 152232 Hom.: 783 Cov.: 32 AF XY: 0.0821 AC XY: 6111 AN XY: 74446

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.0274

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.0560 Hom.: 307

Bravo AF: 0.0876

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16972160; hg19: chr15-80749373;