dbSNP rs3215133: ARNT:c.1032+107delA (chr1-150829796-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001668.4(ARNT):c.1032+107delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 1,210,486 control chromosomes in the GnomAD database, including 6,760 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.081 ( 750 hom., cov: 31)

Exomes 𝑓: 0.097 ( 6010 hom. )

Consequence

ARNT
NM_001668.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

4 publications found

Variant links:

COSMIC-nc: COSV62231061

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.1032+107delA		intron_variant	Intron 11 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.1032+107delA		intron_variant	Intron 11 of 21	1	NM_001668.4	ENSP00000351407.5		P27540-1
ARNT	ENST00000471844.6 link	n.1032+107delA		intron_variant	Intron 11 of 16	2		ENSP00000425899.1		A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

12359

AN:

152162

Hom.:

747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0662

GnomAD4 exome

AF:

0.0974

AC:

103032

AN:

1058206

Hom.:

6010

AF XY:

0.0946

AC XY:

50470

AN XY:

533544

show subpopulations

African (AFR)

AF:

0.0169

AC:

418

AN:

24754

American (AMR)

AF:

0.183

AC:

5681

AN:

30972

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

785

AN:

20954

East Asian (EAS)

AF:

0.00910

AC:

331

AN:

36370

South Asian (SAS)

AF:

0.0337

AC:

2294

AN:

68112

European-Finnish (FIN)

AF:

0.166

AC:

7254

AN:

43582

Middle Eastern (MID)

AF:

0.0176

AC:

AN:

4882

European-Non Finnish (NFE)

AF:

0.105

AC:

82278

AN:

782076

Other (OTH)

AF:

0.0840

AC:

3905

AN:

46504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4421

8842

13263

17684

22105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2676

5352

8028

10704

13380

<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:

0.0812

AC:

12363

AN:

152280

Hom.:

750

Cov.:

AF XY:

0.0852

AC XY:

6343

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0202

AC:

839

AN:

41584

American (AMR)

AF:

0.148

AC:

2262

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3472

East Asian (EAS)

AF:

0.00424

AC:

AN:

5186

South Asian (SAS)

AF:

0.0286

AC:

138

AN:

4830

European-Finnish (FIN)

AF:

0.167

AC:

1774

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

6985

AN:

68014

Other (OTH)

AF:

0.0655

AC:

138

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

563

1126

1688

2251

2814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0384

Hom.:

Bravo

AF:

0.0781

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.2

Mutation Taster

=97/3

polymorphism

(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