rs11589458

Positions:

• chr1-150820140-A-G
• chr1-150820140-A-T

Variant summary

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

The NM_001668.4(ARNT):​c.1395-2110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,990 control chromosomes in the GnomAD database, including 8,967 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 0.33 (8967 hom., cov: 31)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.1395-2110T>C		intron_variant		ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.1395-2110T>C		intron_variant		1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.1243-2110T>C		intron_variant		2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50856 AN: 151872 Hom.: 8961 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.335 AC: 50867 AN: 151990 Hom.: 8967 Cov.: 31 AF XY: 0.341 AC XY: 25352 AN XY: 74284

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.353

Alfa AF: 0.344 Hom.: 10435

Bravo AF: 0.328

Asia WGS AF: 0.408 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.74

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: rs11589458; hg19: chr1-150792616;