15-80452311-C-T

Variant names:

• chr15-80452311-C-T
• rs3848174
• NM_014862.4:c.146+1317C>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.146+1317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,048 control chromosomes in the GnomAD database, including 9,187 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 0.32 (9187 hom., cov: 32)
• Consequence: ARNT2 NM_014862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 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.146+1317C>T		intron	N/A	NP_055677.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT2	ENST00000303329.9	TSL:1 MANE Select	c.146+1317C>T		intron	N/A	ENSP00000307479.4	Q9HBZ2-1
	ARNT2	ENST00000529181.1	TSL:1	n.312+1317C>T		intron	N/A
	ARNT2	ENST00000869656.1		c.146+1317C>T		intron	N/A	ENSP00000539715.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48644 AN: 151928 Hom.: 9183 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.320 AC: 48667 AN: 152048 Hom.: 9187 Cov.: 32 AF XY: 0.328 AC XY: 24346 AN XY: 74296

African (AFR) AF: 0.120 AC: 4983 AN: 41512

American (AMR) AF: 0.437 AC: 6672 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3464

East Asian (EAS) AF: 0.556 AC: 2862 AN: 5152

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4814

European-Finnish (FIN) AF: 0.479 AC: 5057 AN: 10564

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25395 AN: 67958

Other (OTH) AF: 0.324 AC: 683 AN: 2106

Alfa AF: 0.334 Hom.: 1207

Bravo AF: 0.315

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.026
DANN	Benign	0.79
PhyloP100		-0.98
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: rs3848174; hg19: chr15-80744652;