rs1139651

Variant names:

• chr15-80597665-G-A
• rs1139651
• NM_014862.4:c.*3967G>A

Variant summary

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

The NM_014862.4(ARNT2):​c.*3967G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 157,822 control chromosomes in the GnomAD database, including 1,921 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 0.14 (1861 hom., cov: 32)
  • Exomes 𝑓: 0.11 (60 hom.)
• Consequence: ARNT2 NM_014862.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae)
• 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 (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014862.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT2	NM_014862.4	MANE Select	c.*3967G>A		3_prime_UTR	Exon 19 of 19	NP_055677.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT2	ENST00000303329.9	TSL:1 MANE Select	c.*3967G>A		3_prime_UTR	Exon 19 of 19	ENSP00000307479.4	Q9HBZ2-1
	ARNT2	ENST00000869656.1		c.*3967G>A		3_prime_UTR	Exon 20 of 20	ENSP00000539715.1
	ARNT2	ENST00000869655.1		c.*3967G>A		3_prime_UTR	Exon 19 of 19	ENSP00000539714.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20973 AN: 152054 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.112 AC: 632 AN: 5650 Hom.: 60 Cov.: 0 AF XY: 0.114 AC XY: 337 AN XY: 2962

African (AFR) AF: 0.341 AC: 30 AN: 88

American (AMR) AF: 0.202 AC: 178 AN: 882

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 10 AN: 70

East Asian (EAS) AF: 0.0946 AC: 35 AN: 370

South Asian (SAS) AF: 0.167 AC: 77 AN: 460

European-Finnish (FIN) AF: 0.0810 AC: 41 AN: 506

Middle Eastern (MID) AF: 0.100 AC: 1 AN: 10

European-Non Finnish (NFE) AF: 0.0794 AC: 239 AN: 3010

Other (OTH) AF: 0.0827 AC: 21 AN: 254

GnomAD4 genome AF: 0.138 AC: 21015 AN: 152172 Hom.: 1861 Cov.: 32 AF XY: 0.140 AC XY: 10400 AN XY: 74386

African (AFR) AF: 0.248 AC: 10310 AN: 41504

American (AMR) AF: 0.153 AC: 2340 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3472

East Asian (EAS) AF: 0.110 AC: 569 AN: 5166

South Asian (SAS) AF: 0.150 AC: 725 AN: 4820

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5144 AN: 67990

Other (OTH) AF: 0.122 AC: 257 AN: 2112

Alfa AF: 0.0977 Hom.: 3800

Bravo AF: 0.147

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.012
DANN	Benign	0.55
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1139651; hg19: chr15-80890006;