rs2134688

Variant names:

• chr1-150844410-G-A
• rs2134688
• NM_001668.4:c.227+1853C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.227+1853C>T		intron_variant	Intron 4 of 21	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.227+1853C>T		intron_variant	Intron 4 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.227+1853C>T		intron_variant	Intron 4 of 16	2		ENSP00000425899.1

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

African (AFR) AF: 0.673 AC: 27844 AN: 41364

American (AMR) AF: 0.893 AC: 13633 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2954 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4178 AN: 5178

South Asian (SAS) AF: 0.873 AC: 4215 AN: 4828

European-Finnish (FIN) AF: 0.903 AC: 9553 AN: 10574

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61517 AN: 68004

Other (OTH) AF: 0.854 AC: 1801 AN: 2110

Alfa AF: 0.877 Hom.: 177598

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
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2134688; hg19: chr1-150816886;