Genetic Variant ARNT2:c.*4062T>C (chr15-80597760-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.*4062T>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 0.397 in 155,572 control chromosomes in the GnomAD database, including 15,052 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 0.40 ( 14891 hom., cov: 33)

Exomes 𝑓: 0.29 ( 161 hom. )

Consequence

ARNT2
NM_014862.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

Publications

11 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: G2P, Labcorp Genetics (formerly Invitae)
septooptic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ARNT2 links:

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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=-0.64).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 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.*4062T>C		3_prime_UTR	Exon 19 of 19	NP_055677.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARNT2	ENST00000303329.9	TSL:1 MANE Select	c.*4062T>C	3_prime_UTR	Exon 19 of 19	ENSP00000307479.4	Q9HBZ2-1
ARNT2	ENST00000869656.1		c.*4062T>C	3_prime_UTR	Exon 20 of 20	ENSP00000539715.1
ARNT2	ENST00000869655.1		c.*4062T>C	3_prime_UTR	Exon 19 of 19	ENSP00000539714.1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60641

AN:

152092

Hom.:

14847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.293

AC:

985

AN:

3362

Hom.:

161

Cov.:

AF XY:

0.287

AC XY:

500

AN XY:

1744

show subpopulations

African (AFR)

AF:

0.636

AC:

AN:

American (AMR)

AF:

0.371

AC:

213

AN:

574

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

AN:

East Asian (EAS)

AF:

0.101

AC:

AN:

138

South Asian (SAS)

AF:

0.356

AC:

AN:

216

European-Finnish (FIN)

AF:

0.232

AC:

103

AN:

444

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.283

AC:

520

AN:

1840

Other (OTH)

AF:

0.345

AC:

AN:

110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

107

143

179

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:

0.399

AC:

60750

AN:

152210

Hom.:

14891

Cov.:

AF XY:

0.396

AC XY:

29485

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.698

AC:

28968

AN:

41506

American (AMR)

AF:

0.365

AC:

5587

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1049

AN:

3466

East Asian (EAS)

AF:

0.127

AC:

657

AN:

5192

South Asian (SAS)

AF:

0.374

AC:

1802

AN:

4816

European-Finnish (FIN)

AF:

0.251

AC:

2662

AN:

10610

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18852

AN:

68006

Other (OTH)

AF:

0.351

AC:

742

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1652

3303

4955

6606

8258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.320

Hom.:

14968

Bravo

AF:

0.420

Asia WGS

AF:

0.264

AC:

917

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over