rs2134688

Positions:

• chr1-150844410-G-A

Variant summary

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

The NM_001668.4(ARNT):​c.227+1853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,002 control chromosomes in the GnomAD database, including 53,653 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 0.83 (53653 hom., cov: 30)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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 (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT	NM_001668.4	c.227+1853C>T		intron_variant		ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.227+1853C>T		intron_variant		1	NM_001668.4	P3

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126685 AN: 151884 Hom.: 53644 Cov.: 30

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.854

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.834 AC: 126735 AN: 152002 Hom.: 53653 Cov.: 30 AF XY: 0.836 AC XY: 62125 AN XY: 74320

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.903

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.854

Alfa AF: 0.891 Hom.: 79763

Bravo AF: 0.824

Asia WGS AF: 0.826 AC: 2871 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.48

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: rs2134688; hg19: chr1-150816886;