Genetic Variant ARNT:p.Gln769Glu (chr1-150812086-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001668.4(ARNT):c.2305C>G(p.Gln769Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000413 in 1,573,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ARNT
NM_001668.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17455608).

BS2

High AC in GnomAd4 at 6 AD gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ARNT	NM_001668.4	MANE Select	c.2305C>G	p.Gln769Glu	missense	Exon 22 of 22	NP_001659.1	P27540-1
ARNT	NM_001350225.2		c.2302C>G	p.Gln768Glu	missense	Exon 22 of 22	NP_001337154.1
ARNT	NM_001286036.2		c.2299C>G	p.Gln767Glu	missense	Exon 22 of 22	NP_001272965.1	P27540-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARNT	ENST00000358595.10	TSL:1 MANE Select	c.2305C>G	p.Gln769Glu	missense	Exon 22 of 22	ENSP00000351407.5	P27540-1
ARNT	ENST00000354396.6	TSL:1	c.2299C>G	p.Gln767Glu	missense	Exon 22 of 22	ENSP00000346372.2	P27540-4
ARNT	ENST00000515192.5	TSL:1	c.2263C>G	p.Gln755Glu	missense	Exon 23 of 23	ENSP00000423851.1	P27540-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000348

AC:

AN:

229638

AF XY:

0.0000241

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000657

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000415

AC:

AN:

1420758

Hom.:

Cov.:

AF XY:

0.0000382

AC XY:

AN XY:

706388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31922

American (AMR)

AF:

0.00

AC:

AN:

40512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25380

East Asian (EAS)

AF:

0.00

AC:

AN:

36938

South Asian (SAS)

AF:

0.00

AC:

AN:

80318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.0000523

AC:

AN:

1088972

Other (OTH)

AF:

0.0000342

AC:

AN:

58420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000394

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41544

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

PhyloP100

6.8

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.2

REVEL

Benign

0.20

Sift

Benign

0.14

Sift4G

Benign

0.34

Polyphen

0.97

Vest4

0.55

MVP

0.52

MPC

1.0

ClinPred

0.52

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.19

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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