Genetic Variant ARNT:c.486+123A>G (chr1-150839318-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_001668.4(ARNT):c.486+123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 882,142 control chromosomes in the GnomAD database, including 71,383 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 0.42 ( 13804 hom., cov: 32)

Exomes 𝑓: 0.39 ( 57579 hom. )

Consequence

ARNT
NM_001668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.612

Publications

23 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.486+123A>G		intron_variant	Intron 6 of 21	ENST00000358595.10	NP_001659.1	P27540-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10 link	c.486+123A>G		intron_variant	Intron 6 of 21	1	NM_001668.4	ENSP00000351407.5		P27540-1
ARNT	ENST00000471844.6 link	n.486+123A>G		intron_variant	Intron 6 of 16	2		ENSP00000425899.1		A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63690

AN:

151972

Hom.:

13791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.414

GnomAD4 exome

AF:

0.393

AC:

286832

AN:

730052

Hom.:

57579

AF XY:

0.398

AC XY:

149813

AN XY:

376016

show subpopulations

African (AFR)

AF:

0.513

AC:

9443

AN:

18404

American (AMR)

AF:

0.431

AC:

10977

AN:

25484

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

7835

AN:

16530

East Asian (EAS)

AF:

0.380

AC:

13380

AN:

35238

South Asian (SAS)

AF:

0.535

AC:

29661

AN:

55468

European-Finnish (FIN)

AF:

0.351

AC:

15291

AN:

43578

Middle Eastern (MID)

AF:

0.453

AC:

1430

AN:

3154

European-Non Finnish (NFE)

AF:

0.371

AC:

184311

AN:

496672

Other (OTH)

AF:

0.408

AC:

14504

AN:

35524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9240

18481

27721

36962

46202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.419

AC:

63732

AN:

152090

Hom.:

13804

Cov.:

AF XY:

0.422

AC XY:

31389

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.501

AC:

20792

AN:

41488

American (AMR)

AF:

0.442

AC:

6755

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.479

AC:

1663

AN:

3470

East Asian (EAS)

AF:

0.388

AC:

2012

AN:

5180

South Asian (SAS)

AF:

0.542

AC:

2612

AN:

4818

European-Finnish (FIN)

AF:

0.345

AC:

3643

AN:

10562

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

24999

AN:

67982

Other (OTH)

AF:

0.418

AC:

882

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1905

3810

5715

7620

9525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.401

Hom.:

2037

Bravo

AF:

0.423

Asia WGS

AF:

0.430

AC:

1492

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

1.7

(source)

DANN

Benign

0.37

PhyloP100

-0.61

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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1-150839318-T-C

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