dbSNP rs10305650: ARNT:c.25+42C>T (chr1-150876501-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_001668.4(ARNT):c.25+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,547,072 control chromosomes in the GnomAD database, including 1,687 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 0.060 ( 942 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 745 hom. )

Consequence

ARNT
NM_001668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.41

Publications

2 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.25+42C>T		intron_variant	Intron 1 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.25+42C>T		intron_variant	Intron 1 of 21	1	NM_001668.4	ENSP00000351407.5		P27540-1
ARNT	ENST00000471844.6 link	n.25+42C>T		intron_variant	Intron 1 of 16	2		ENSP00000425899.1		A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.0599

AC:

9099

AN:

152006

Hom.:

941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0431

GnomAD2 exomes

AF:

0.0129

AC:

1922

AN:

149530

AF XY:

0.00980

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.00915

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00624

AC:

8705

AN:

1394950

Hom.:

745

Cov.:

AF XY:

0.00543

AC XY:

3739

AN XY:

688152

show subpopulations

African (AFR)

AF:

0.212

AC:

6599

AN:

31108

American (AMR)

AF:

0.0115

AC:

411

AN:

35612

Ashkenazi Jewish (ASJ)

AF:

0.000160

AC:

AN:

25034

East Asian (EAS)

AF:

0.00

AC:

AN:

35374

South Asian (SAS)

AF:

0.000746

AC:

AN:

79118

European-Finnish (FIN)

AF:

0.0000205

AC:

AN:

48830

Middle Eastern (MID)

AF:

0.0219

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

0.000679

AC:

732

AN:

1078086

Other (OTH)

AF:

0.0140

AC:

810

AN:

57722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0599

AC:

9113

AN:

152122

Hom.:

942

Cov.:

AF XY:

0.0578

AC XY:

4300

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.208

AC:

8609

AN:

41444

American (AMR)

AF:

0.0212

AC:

324

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00110

AC:

AN:

68006

Other (OTH)

AF:

0.0427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

336

672

1008

1344

1680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0330

Hom.:

Bravo

AF:

0.0689

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

2.4

PromoterAI

0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over