rs2256355

Positions:

• chr1-150839318-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001668.4(ARNT):​c.486+123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 882,142 control chromosomes in the GnomAD database, including 71,383 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 0.42 (13804 hom., cov: 32)
  • Exomes 𝑓: 0.39 (57579 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.486+123A>G		intron_variant		ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.486+123A>G		intron_variant		1	NM_001668.4	ENSP00000351407	P3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63690 AN: 151972 Hom.: 13791 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.393 AC: 286832 AN: 730052 Hom.: 57579 AF XY: 0.398 AC XY: 149813 AN XY: 376016

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.419 AC: 63732 AN: 152090 Hom.: 13804 Cov.: 32 AF XY: 0.422 AC XY: 31389 AN XY: 74336

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.418

Alfa AF: 0.397 Hom.: 1930

Bravo AF: 0.423

Asia WGS AF: 0.430 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.37

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: rs2256355; hg19: chr1-150811794; COSMIC: COSV62230099; COSMIC: COSV62230099;