Genetic Variant ARNT:c.956-540A>G (chr1-150830520-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.956-540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,132 control chromosomes in the GnomAD database, including 9,370 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 0.34 ( 9367 hom., cov: 32)

Exomes 𝑓: 0.31 ( 3 hom. )

Consequence

ARNT
NM_001668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

11 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 = 0.516 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.956-540A>G	intron	N/A	NP_001659.1	P27540-1
ARNT	NM_001350225.2		c.953-540A>G	intron	N/A	NP_001337154.1
ARNT	NM_001286036.2		c.956-540A>G	intron	N/A	NP_001272965.1	P27540-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARNT	ENST00000358595.10	TSL:1 MANE Select	c.956-540A>G	intron	N/A	ENSP00000351407.5	P27540-1
ARNT	ENST00000354396.6	TSL:1	c.956-540A>G	intron	N/A	ENSP00000346372.2	P27540-4
ARNT	ENST00000515192.5	TSL:1	c.929-555A>G	intron	N/A	ENSP00000423851.1	P27540-3

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52388

AN:

151944

Hom.:

9359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.314

AC:

AN:

Hom.:

AF XY:

0.262

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.259

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.591

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.345

AC:

52404

AN:

152062

Hom.:

9367

Cov.:

AF XY:

0.350

AC XY:

26055

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.269

AC:

11154

AN:

41472

American (AMR)

AF:

0.409

AC:

6241

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1519

AN:

3468

East Asian (EAS)

AF:

0.388

AC:

2008

AN:

5178

South Asian (SAS)

AF:

0.534

AC:

2571

AN:

4818

European-Finnish (FIN)

AF:

0.341

AC:

3602

AN:

10550

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24187

AN:

67984

Other (OTH)

AF:

0.360

AC:

761

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1754

3508

5263

7017

8771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.246

Hom.:

788

Bravo

AF:

0.340

Asia WGS

AF:

0.410

AC:

1422

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.6

(source)

DANN

Benign

0.77

PhyloP100

0.034

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over