Genetic Variant ARNT:c.1167+103A>G (chr1-150828990-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.1167+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,343,280 control chromosomes in the GnomAD database, including 539,884 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 0.84 ( 54422 hom., cov: 32)

Exomes 𝑓: 0.90 ( 485462 hom. )

Consequence

ARNT
NM_001668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200

Publications

17 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.1167+103A>G		intron_variant	Intron 12 of 21	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10 link	c.1167+103A>G		intron_variant	Intron 12 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6 link	n.1167+103A>G		intron_variant	Intron 12 of 16	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes

AF:

0.841

AC:

127887

AN:

152116

Hom.:

54409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.697

Gnomad AMI

AF:

0.871

Gnomad AMR

AF:

0.896

Gnomad ASJ

AF:

0.851

Gnomad EAS

AF:

0.809

Gnomad SAS

AF:

0.873

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.905

Gnomad OTH

AF:

0.859

GnomAD4 exome

AF:

0.902

AC:

1073937

AN:

1191048

Hom.:

485462

AF XY:

0.901

AC XY:

528171

AN XY:

586440

show subpopulations

African (AFR)

AF:

0.687

AC:

18344

AN:

26692

American (AMR)

AF:

0.919

AC:

22782

AN:

24800

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

15978

AN:

18938

East Asian (EAS)

AF:

0.816

AC:

29886

AN:

36618

South Asian (SAS)

AF:

0.874

AC:

51547

AN:

59002

European-Finnish (FIN)

AF:

0.904

AC:

40374

AN:

44638

Middle Eastern (MID)

AF:

0.860

AC:

4257

AN:

4952

European-Non Finnish (NFE)

AF:

0.915

AC:

846005

AN:

924948

Other (OTH)

AF:

0.887

AC:

44764

AN:

50460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4920

9841

14761

19682

24602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17950

35900

53850

71800

89750

<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:

0.840

AC:

127942

AN:

152232

Hom.:

54422

Cov.:

AF XY:

0.843

AC XY:

62726

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.696

AC:

28895

AN:

41504

American (AMR)

AF:

0.896

AC:

13712

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.851

AC:

2954

AN:

3472

East Asian (EAS)

AF:

0.808

AC:

4186

AN:

5180

South Asian (SAS)

AF:

0.873

AC:

4213

AN:

4824

European-Finnish (FIN)

AF:

0.904

AC:

9585

AN:

10604

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.905

AC:

61542

AN:

68030

Other (OTH)

AF:

0.858

AC:

1811

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

974

1948

2922

3896

4870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.886

Hom.:

99573

Bravo

AF:

0.831

Asia WGS

AF:

0.828

AC:

2881

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.7

(source)

DANN

Benign

0.74

PhyloP100

0.20

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