Genetic Variant ARNT:c.486+205A>G (chr1-150839236-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001668.4(ARNT):c.486+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,080 control chromosomes in the GnomAD database, including 9,486 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 0.35 ( 9486 hom., cov: 32)

Consequence

ARNT
NM_001668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

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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new If you want to explore the variant's impact on the transcript NM_001668.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

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.486+205A>G	intron	N/A	NP_001659.1	P27540-1
ARNT	NM_001350225.2		c.483+205A>G	intron	N/A	NP_001337154.1
ARNT	NM_001286036.2		c.486+205A>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.486+205A>G	intron	N/A	ENSP00000351407.5	P27540-1
ARNT	ENST00000354396.6	TSL:1	c.486+205A>G	intron	N/A	ENSP00000346372.2	P27540-4
ARNT	ENST00000515192.5	TSL:1	c.459+205A>G	intron	N/A	ENSP00000423851.1	P27540-3

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52800

AN:

151964

Hom.:

9479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.347

AC:

52814

AN:

152080

Hom.:

9486

Cov.:

AF XY:

0.353

AC XY:

26238

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.277

AC:

11509

AN:

41484

American (AMR)

AF:

0.410

AC:

6263

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1530

AN:

3470

East Asian (EAS)

AF:

0.388

AC:

2004

AN:

5170

South Asian (SAS)

AF:

0.534

AC:

2573

AN:

4822

European-Finnish (FIN)

AF:

0.342

AC:

3612

AN:

10558

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24199

AN:

67980

Other (OTH)

AF:

0.361

AC:

762

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1747

3494

5242

6989

8736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.346

Hom.:

1267

Bravo

AF:

0.343

Asia WGS

AF:

0.412

AC:

1432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.3

(source)

DANN

Benign

0.84

PhyloP100

0.047

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over