Genetic Variant ARNT:n.*899A>G (chr1-150811509-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 ENST00000471844.6(ARNT):n.*899A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 233,042 control chromosomes in the GnomAD database, including 15,011 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 0.35 ( 9381 hom., cov: 31)

Exomes 𝑓: 0.37 ( 5630 hom. )

Consequence

ARNT
ENST00000471844.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.59

Publications

27 publications found

Variant links:

Genes affected

ARNT (HGNC:700): (aryl hydrocarbon receptor nuclear translocator) This gene encodes a protein containing a basic helix-loop-helix domain and two characteristic PAS domains along with a PAC domain. The encoded protein binds to ligand-bound aryl hydrocarbon receptor and aids in the movement of this complex to the nucleus, where it promotes the expression of genes involved in xenobiotic metabolism. This protein is also a co-factor for transcriptional regulation by hypoxia-inducible factor 1. Chromosomal translocation of this locus with the ETV6 (ets variant 6) gene on chromosome 12 have been described in leukemias. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

ARNT 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=-0.72).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.*512A>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000358595.10	NP_001659.1	P27540-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARNT	ENST00000471844.6 link	n.*899A>G	non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000425899.1	A6NGV6
ARNT	ENST00000358595.10 link	c.*512A>G	3_prime_UTR_variant	Exon 22 of 22	1	NM_001668.4	ENSP00000351407.5	P27540-1
ARNT	ENST00000471844.6 link	n.*899A>G	3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000425899.1	A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52438

AN:

151550

Hom.:

9373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.371

AC:

30170

AN:

81374

Hom.:

5630

Cov.:

AF XY:

0.374

AC XY:

14037

AN XY:

37526

show subpopulations

African (AFR)

AF:

0.275

AC:

1072

AN:

3894

American (AMR)

AF:

0.385

AC:

966

AN:

2506

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

2210

AN:

5126

East Asian (EAS)

AF:

0.390

AC:

4482

AN:

11506

South Asian (SAS)

AF:

0.523

AC:

367

AN:

702

European-Finnish (FIN)

AF:

0.350

AC:

128

AN:

366

Middle Eastern (MID)

AF:

0.425

AC:

210

AN:

494

European-Non Finnish (NFE)

AF:

0.364

AC:

18198

AN:

50018

Other (OTH)

AF:

0.375

AC:

2537

AN:

6762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1095

2190

3286

4381

5476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.346

AC:

52454

AN:

151668

Hom.:

9381

Cov.:

AF XY:

0.351

AC XY:

26062

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.272

AC:

11243

AN:

41314

American (AMR)

AF:

0.408

AC:

6221

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1519

AN:

3464

East Asian (EAS)

AF:

0.389

AC:

1997

AN:

5138

South Asian (SAS)

AF:

0.535

AC:

2568

AN:

4800

European-Finnish (FIN)

AF:

0.344

AC:

3614

AN:

10520

Middle Eastern (MID)

AF:

0.404

AC:

118

AN:

292

European-Non Finnish (NFE)

AF:

0.356

AC:

24178

AN:

67886

Other (OTH)

AF:

0.360

AC:

759

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1764

3528

5291

7055

8819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.354

Hom.:

24130

Bravo

AF:

0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.15

(source)

DANN

Benign

0.80

PhyloP100

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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