rs12439920

Variant names:

• chr15-80512400-A-G
• rs12439920
• NM_014862.4:c.726-1511A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-80512400-A-G
• chr15-80512400-A-T

Variant summary

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

The NM_014862.4(ARNT2):​c.726-1511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,276 control chromosomes in the GnomAD database, including 62,051 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 0.90 (62051 hom., cov: 33)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 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 Gene-Disease associations (from GenCC):

• Webb-Dattani syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• septooptic dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.726-1511A>G		intron_variant	Intron 6 of 18	ENST00000303329.9	NP_055677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9	c.726-1511A>G		intron_variant	Intron 6 of 18	1	NM_014862.4	ENSP00000307479.4
ARNT2	ENST00000527771.5	c.693-1511A>G		intron_variant	Intron 6 of 18	2		ENSP00000453792.1
ARNT2	ENST00000533983.5	c.693-1511A>G		intron_variant	Intron 7 of 19	5		ENSP00000453651.1
ARNT2	ENST00000525103.1	c.48-1511A>G		intron_variant	Intron 2 of 5	3		ENSP00000452961.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137079 AN: 152158 Hom.: 61997 Cov.: 33

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.901 AC: 137188 AN: 152276 Hom.: 62051 Cov.: 33 AF XY: 0.902 AC XY: 67178 AN XY: 74458

African (AFR) AF: 0.970 AC: 40343 AN: 41570

American (AMR) AF: 0.815 AC: 12463 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3115 AN: 3470

East Asian (EAS) AF: 0.992 AC: 5148 AN: 5190

South Asian (SAS) AF: 0.865 AC: 4165 AN: 4814

European-Finnish (FIN) AF: 0.940 AC: 9975 AN: 10612

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59095 AN: 68020

Other (OTH) AF: 0.887 AC: 1872 AN: 2110

Alfa AF: 0.886 Hom.: 19583

Bravo AF: 0.893

Asia WGS AF: 0.921 AC: 3205 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	0.082
DANN	Benign	0.56
PhyloP100		-1.4
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: rs12439920; hg19: chr15-80804741;