rs3215133

Positions:

• chr1-150829796-AT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001668.4(ARNT):​c.1032+107delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 1,210,486 control chromosomes in the GnomAD database, including 6,760 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.081 (750 hom., cov: 31)
  • Exomes 𝑓: 0.097 (6010 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.1032+107delA		intron_variant		ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.1032+107delA		intron_variant		1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.1032+107delA		intron_variant		2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12359 AN: 152162 Hom.: 747 Cov.: 31

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0662

GnomAD4 exome AF: 0.0974 AC: 103032 AN: 1058206 Hom.: 6010 AF XY: 0.0946 AC XY: 50470 AN XY: 533544

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.0375

Gnomad4 EAS exome AF: 0.00910

Gnomad4 SAS exome AF: 0.0337

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0840

GnomAD4 genome AF: 0.0812 AC: 12363 AN: 152280 Hom.: 750 Cov.: 31 AF XY: 0.0852 AC XY: 6343 AN XY: 74438

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0655

Alfa AF: 0.0384 Hom.: 42

Bravo AF: 0.0781

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3215133; hg19: chr1-150802272; COSMIC: COSV62231061; COSMIC: COSV62231061;