Genetic Variant NM_014862.4:c.*3967G>A (chr15-80597665-G-A) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

7 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT2	NM_014862.4 link	c.*3967G>A		3_prime_UTR_variant	Exon 19 of 19	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.*3967G>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_014862.4	ENSP00000307479.4		Q9HBZ2-1
ARNT2	ENST00000533983.5 link	c.*3967G>A		3_prime_UTR_variant	Exon 20 of 20	5		ENSP00000453651.1		Q9HBZ2-2

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20973

AN:

152054

Hom.:

1849

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.114

AC XY:

337

AN XY:

2962

show subpopulations

African (AFR)

AF:

0.341

AC:

AN:

American (AMR)

AF:

0.202

AC:

178

AN:

882

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

AN:

East Asian (EAS)

AF:

0.0946

AC:

AN:

370

South Asian (SAS)

AF:

0.167

AC:

AN:

460

European-Finnish (FIN)

AF:

0.0810

AC:

AN:

506

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0794

AC:

239

AN:

3010

Other (OTH)

AF:

0.0827

AC:

AN:

254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.138

AC:

21015

AN:

152172

Hom.:

1861

Cov.:

AF XY:

0.140

AC XY:

10400

AN XY:

74386

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0757

AC:

5144

AN:

67990

Other (OTH)

AF:

0.122

AC:

257

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

886

1772

2658

3544

4430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.0977

Hom.:

3800

Bravo

AF:

0.147

Asia WGS

AF:

0.134

AC:

466

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.012

(source)

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)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over