Genetic Variant ARNT:c.*1039G>A (chr1-150810982-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001668.4(ARNT):c.*1039G>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 0.0367 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
NM_001668.4 3_prime_UTR

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:

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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=-0.73).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001668.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARNT	NM_001668.4	MANE Select	c.*1039G>A	3_prime_UTR	Exon 22 of 22	NP_001659.1	P27540-1
ARNT	NM_001350225.2		c.*1039G>A	3_prime_UTR	Exon 22 of 22	NP_001337154.1
ARNT	NM_001286036.2		c.*1039G>A	3_prime_UTR	Exon 22 of 22	NP_001272965.1	P27540-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARNT	ENST00000358595.10	TSL:1 MANE Select	c.*1039G>A	3_prime_UTR	Exon 22 of 22	ENSP00000351407.5	P27540-1
ARNT	ENST00000354396.6	TSL:1	c.*1039G>A	3_prime_UTR	Exon 22 of 22	ENSP00000346372.2	P27540-4
ARNT	ENST00000471844.6	TSL:2	n.*1426G>A	non_coding_transcript_exon	Exon 17 of 17	ENSP00000425899.1	A6NGV6

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 v4.9

Name

Calibrated prediction

Score

Prediction

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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