ENST00000471844.6:n.*1426G>A – 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.*1426G>A 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 0.0367 in 229,814 control chromosomes in the GnomAD database, including 407 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 0.046 ( 375 hom., cov: 32)

Exomes 𝑓: 0.019 ( 32 hom. )

Consequence

ARNT
ENST00000471844.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.385

Publications

9 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:

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=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.*1039G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ARNT	ENST00000471844.6 link	n.*1426G>A	non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000425899.1
ARNT	ENST00000358595.10 link	c.*1039G>A	3_prime_UTR_variant	Exon 22 of 22	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000354396.6 link	c.*1039G>A	3_prime_UTR_variant	Exon 22 of 22	1		ENSP00000346372.2
ARNT	ENST00000471844.6 link	n.*1426G>A	3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6936

AN:

152120

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0222

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00809

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0402

GnomAD4 exome

AF:

0.0193

AC:

1500

AN:

77576

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

638

AN XY:

35768

show subpopulations

African (AFR)

AF:

0.129

AC:

476

AN:

3680

American (AMR)

AF:

0.0265

AC:

AN:

2380

Ashkenazi Jewish (ASJ)

AF:

0.0372

AC:

181

AN:

4870

East Asian (EAS)

AF:

0.0000906

AC:

AN:

11032

South Asian (SAS)

AF:

0.00455

AC:

AN:

660

European-Finnish (FIN)

AF:

0.00435

AC:

AN:

460

Middle Eastern (MID)

AF:

0.0234

AC:

AN:

470

European-Non Finnish (NFE)

AF:

0.0126

AC:

601

AN:

47600

Other (OTH)

AF:

0.0252

AC:

162

AN:

6424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0456

AC:

6939

AN:

152238

Hom.:

375

Cov.:

AF XY:

0.0444

AC XY:

3308

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.133

AC:

5541

AN:

41526

American (AMR)

AF:

0.0222

AC:

339

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00810

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

770

AN:

68028

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

320

640

959

1279

1599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0257

Hom.:

399

Bravo

AF:

0.0523

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.5

(source)

DANN

Benign

0.80

PhyloP100

-0.39

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