Genetic Variant ARNT:c.272+98T>C (chr1-150842326-A-G) – 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.272+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,509,356 control chromosomes in the GnomAD database, including 1,645 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 0.060 ( 939 hom., cov: 31)

Exomes 𝑓: 0.0060 ( 706 hom. )

Consequence

ARNT
NM_001668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10

Publications

1 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=-0.54).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.272+98T>C		intron_variant	Intron 5 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.272+98T>C		intron_variant	Intron 5 of 21	1	NM_001668.4	ENSP00000351407.5		P27540-1
ARNT	ENST00000471844.6 link	n.272+98T>C		intron_variant	Intron 5 of 16	2		ENSP00000425899.1		A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

9094

AN:

152122

Hom.:

939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.0425

GnomAD4 exome

AF:

0.00602

AC:

8175

AN:

1357116

Hom.:

706

Cov.:

AF XY:

0.00530

AC XY:

3557

AN XY:

671764

show subpopulations

African (AFR)

AF:

0.213

AC:

6278

AN:

29456

American (AMR)

AF:

0.0116

AC:

352

AN:

30434

Ashkenazi Jewish (ASJ)

AF:

0.0000906

AC:

AN:

22066

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36896

South Asian (SAS)

AF:

0.000676

AC:

AN:

70962

European-Finnish (FIN)

AF:

0.0000211

AC:

AN:

47360

Middle Eastern (MID)

AF:

0.0174

AC:

AN:

5234

European-Non Finnish (NFE)

AF:

0.000657

AC:

696

AN:

1059872

Other (OTH)

AF:

0.0129

AC:

706

AN:

54836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

326

653

979

1306

1632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<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:

0.0598

AC:

9106

AN:

152240

Hom.:

939

Cov.:

AF XY:

0.0577

AC XY:

4297

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.207

AC:

8608

AN:

41502

American (AMR)

AF:

0.0212

AC:

324

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00124

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68020

Other (OTH)

AF:

0.0421

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

365

730

1095

1460

1825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0249

Hom.:

825

Bravo

AF:

0.0688

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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