chr15-80417979-T-C

Variant names:

• chr15-80417979-T-C
• rs7172914
• NM_014862.4:c.31+13433T>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.31+13433T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 151,960 control chromosomes in the GnomAD database, including 42,813 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 0.75 (42813 hom., cov: 30)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT2	NM_014862.4	c.31+13433T>C		intron_variant	Intron 1 of 18	ENST00000303329.9	NP_055677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9	c.31+13433T>C		intron_variant	Intron 1 of 18	1	NM_014862.4	ENSP00000307479.4
ARNT2	ENST00000529181.1	n.197+13433T>C		intron_variant	Intron 1 of 4	1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113645 AN: 151842 Hom.: 42784 Cov.: 30

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.748 AC: 113713 AN: 151960 Hom.: 42813 Cov.: 30 AF XY: 0.741 AC XY: 54998 AN XY: 74240

African (AFR) AF: 0.745 AC: 30852 AN: 41432

American (AMR) AF: 0.638 AC: 9744 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2678 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4133 AN: 5158

South Asian (SAS) AF: 0.722 AC: 3468 AN: 4804

European-Finnish (FIN) AF: 0.654 AC: 6895 AN: 10550

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.789 AC: 53602 AN: 67976

Other (OTH) AF: 0.761 AC: 1599 AN: 2102

Alfa AF: 0.775 Hom.: 172615

Bravo AF: 0.745

Asia WGS AF: 0.719 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		0.14
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: rs7172914; hg19: chr15-80710321; COSMIC: COSV57592276;