Genetic Variant ARNT2:c.31+22499T>C (chr15-80427045-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014862.4(ARNT2):c.31+22499T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,088 control chromosomes in the GnomAD database, including 7,507 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 0.31 ( 7507 hom., cov: 32)

Consequence

ARNT2
NM_014862.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.482

Publications

2 publications found

Variant links:

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

ARNT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT2	NM_014862.4 link	c.31+22499T>C		intron_variant	Intron 1 of 18	ENST00000303329.9	NP_055677.3	Q9HBZ2-1X5DQN9Q7Z3A3Q86TN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT2	ENST00000303329.9 link	c.31+22499T>C		intron_variant	Intron 1 of 18	1	NM_014862.4	ENSP00000307479.4		Q9HBZ2-1
ARNT2	ENST00000529181.1 link	n.197+22499T>C		intron_variant	Intron 1 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47039

AN:

151970

Hom.:

7501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.310

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

GnomAD4 genome

AF:

0.310

AC:

47077

AN:

152088

Hom.:

7507

Cov.:

AF XY:

0.311

AC XY:

23119

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.352

AC:

14598

AN:

41472

American (AMR)

AF:

0.376

AC:

5739

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1003

AN:

3470

East Asian (EAS)

AF:

0.536

AC:

2768

AN:

5164

South Asian (SAS)

AF:

0.360

AC:

1729

AN:

4808

European-Finnish (FIN)

AF:

0.241

AC:

2548

AN:

10586

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17690

AN:

67996

Other (OTH)

AF:

0.308

AC:

649

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1643

3286

4929

6572

8215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.282

Hom.:

9391

Bravo

AF:

0.327

Asia WGS

AF:

0.428

AC:

1486

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.35

(source)

DANN

Benign

0.51

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over