rs10847

chr1-150810321-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001668.4(ARNT):c.*1700G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 230,648 control chromosomes in the GnomAD database, including 5,750 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 0.20 (3652 hom., cov: 31)
  • Exomes 𝑓: 0.22 (2098 hom.)
• Consequence: ARNT NM_001668.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.782

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT	NM_001668.4	c.*1700G>A		3_prime_UTR_variant	22/22	ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.*1700G>A		3_prime_UTR_variant	22/22	1	NM_001668.4	P3
ARNT	ENST00000471844.6	c.*2087G>A		3_prime_UTR_variant, NMD_transcript_variant	17/17	2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30264 AN: 151960 Hom.: 3653 Cov.: 31

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.222 AC: 17465 AN: 78570 Hom.: 2098 Cov.: 0 AF XY: 0.220 AC XY: 7983 AN XY: 36274

Gnomad4 AFR exome AF: 0.0570

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.199 AC: 30265 AN: 152078 Hom.: 3652 Cov.: 31 AF XY: 0.198 AC XY: 14730 AN XY: 74322

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.228

Alfa AF: 0.233 Hom.: 2454

Bravo AF: 0.191

Asia WGS AF: 0.219 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	12
Dann	Benign	0.86

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: rs10847; hg19: chr1-150782797; COSMIC: COSV55014416; COSMIC: COSV55014416;