chr15-80593850-T-C

Variant names:

• chr15-80593850-T-C
• rs8033706
• NM_014862.4:c.*152T>C

Variant summary

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

The NM_014862.4(ARNT2):​c.*152T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 666,536 control chromosomes in the GnomAD database, including 128,489 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 0.66 (35558 hom., cov: 30)
  • Exomes 𝑓: 0.58 (92931 hom.)
• Consequence: ARNT2 NM_014862.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 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.*152T>C		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.*152T>C		3_prime_UTR	Exon 19 of 19	ENSP00000307479.4	Q9HBZ2-1
	ARNT2	ENST00000869656.1		c.*152T>C		3_prime_UTR	Exon 20 of 20	ENSP00000539715.1
	ARNT2	ENST00000869655.1		c.*152T>C		3_prime_UTR	Exon 19 of 19	ENSP00000539714.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99724 AN: 151682 Hom.: 35489 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.581 AC: 299210 AN: 514736 Hom.: 92931 Cov.: 6 AF XY: 0.588 AC XY: 157844 AN XY: 268438

African (AFR) AF: 0.918 AC: 13045 AN: 14208

American (AMR) AF: 0.673 AC: 16136 AN: 23984

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 8976 AN: 15006

East Asian (EAS) AF: 0.946 AC: 29291 AN: 30974

South Asian (SAS) AF: 0.764 AC: 36090 AN: 47242

European-Finnish (FIN) AF: 0.500 AC: 15188 AN: 30362

Middle Eastern (MID) AF: 0.582 AC: 1353 AN: 2326

European-Non Finnish (NFE) AF: 0.504 AC: 162393 AN: 322366

Other (OTH) AF: 0.592 AC: 16738 AN: 28268

GnomAD4 genome AF: 0.658 AC: 99858 AN: 151800 Hom.: 35558 Cov.: 30 AF XY: 0.663 AC XY: 49155 AN XY: 74166

African (AFR) AF: 0.914 AC: 37865 AN: 41428

American (AMR) AF: 0.657 AC: 10025 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2026 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4836 AN: 5128

South Asian (SAS) AF: 0.787 AC: 3762 AN: 4782

European-Finnish (FIN) AF: 0.493 AC: 5188 AN: 10524

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34234 AN: 67880

Other (OTH) AF: 0.624 AC: 1317 AN: 2110

Alfa AF: 0.573 Hom.: 14691

Bravo AF: 0.679

Asia WGS AF: 0.870 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.23
PhyloP100		-0.86
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: rs8033706; hg19: chr15-80886191;