Genetic Variant NM_001668.4:c.-171T>C (chr1-150876738-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001668.4(ARNT):c.-171T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 686,946 control chromosomes in the GnomAD database, including 3 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 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

ARNT
NM_001668.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BS2

High AC in GnomAd4 at 396 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4 link	c.-171T>C		upstream_gene_variant		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.-171T>C		upstream_gene_variant		1	NM_001668.4	ENSP00000351407.5		P27540-1
ARNT	ENST00000471844.6 link	n.-171T>C		upstream_gene_variant		2		ENSP00000425899.1		A6NGV6

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00192

GnomAD4 exome

AF:

0.000236

AC:

126

AN:

534724

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

AN XY:

279942

show subpopulations

African (AFR)

AF:

0.00693

AC:

AN:

12834

American (AMR)

AF:

0.000528

AC:

AN:

18940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14000

East Asian (EAS)

AF:

0.00

AC:

AN:

30240

South Asian (SAS)

AF:

0.00

AC:

AN:

48530

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30664

Middle Eastern (MID)

AF:

0.000475

AC:

AN:

2104

European-Non Finnish (NFE)

AF:

0.0000201

AC:

AN:

348662

Other (OTH)

AF:

0.000661

AC:

AN:

28750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00260

AC:

396

AN:

152222

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

179

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00910

AC:

378

AN:

41542

American (AMR)

AF:

0.000588

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67980

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00208

Hom.:

Bravo

AF:

0.00277

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

(source)

DANN

Benign

0.58

PhyloP100

-0.45

PromoterAI

0.018

Neutral

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over