chr1-150817408-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001668.4(ARNT):c.1531G>A(p.Asp511Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00707 in 1,614,158 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0072 ( 53 hom. )

Consequence

ARNT
NM_001668.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.99

Publications

19 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004409611).

BP6

Variant 1-150817408-C-T is Benign according to our data. Variant chr1-150817408-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.1531G>A	p.Asp511Asn	missense_variant	Exon 16 of 22	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.1531G>A	p.Asp511Asn	missense_variant	Exon 16 of 22	1	NM_001668.4	ENSP00000351407.5		P27540-1
ARNT	ENST00000471844.6 link	n.*94+520G>A		intron_variant	Intron 14 of 16	2		ENSP00000425899.1		A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00763

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00823

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00546

AC:

1372

AN:

251470

AF XY:

0.00540

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00554

Gnomad NFE exome

AF:

0.00818

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.00719

AC:

10513

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

5191

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33480

American (AMR)

AF:

0.00528

AC:

236

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00570

AC:

149

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00154

AC:

133

AN:

86256

European-Finnish (FIN)

AF:

0.00541

AC:

289

AN:

53420

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00825

AC:

9171

AN:

1112006

Other (OTH)

AF:

0.00684

AC:

413

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

544

1089

1633

2178

2722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00590

AC:

898

AN:

152280

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

431

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41566

American (AMR)

AF:

0.00746

AC:

114

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00763

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00823

AC:

560

AN:

68016

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00724

Hom.:

Bravo

AF:

0.00620

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00563

AC:

684

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00853

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARNT: BP4, BS2 -

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

MetaRNN

Benign

0.0044

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

L;L;.;.

PhyloP100

5.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.55

N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.26

B;.;B;B

Vest4

0.17

MVP

0.52

MPC

0.29

ClinPred

0.026

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.28

Mutation Taster

=100/0

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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chr1-150817408-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over