1-150841698-A-G

Variant names:

• chr1-150841698-A-G
• rs2864873
• NM_001668.4:c.272+726T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001668.4(ARNT):​c.272+726T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,038 control chromosomes in the GnomAD database, including 9,908 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 0.35 (9908 hom., cov: 31)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001668.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	NM_001668.4	MANE Select	c.272+726T>C		intron	N/A	NP_001659.1
	ARNT	NM_001350225.2		c.269+726T>C		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.272+726T>C		intron	N/A	NP_001272965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	ENST00000358595.10	TSL:1 MANE Select	c.272+726T>C		intron	N/A	ENSP00000351407.5
	ARNT	ENST00000354396.6	TSL:1	c.272+726T>C		intron	N/A	ENSP00000346372.2
	ARNT	ENST00000515192.5	TSL:1	c.245+726T>C		intron	N/A	ENSP00000423851.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53803 AN: 151920 Hom.: 9900 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.354 AC: 53828 AN: 152038 Hom.: 9908 Cov.: 31 AF XY: 0.359 AC XY: 26687 AN XY: 74304

African (AFR) AF: 0.276 AC: 11463 AN: 41476

American (AMR) AF: 0.419 AC: 6401 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1659 AN: 3466

East Asian (EAS) AF: 0.387 AC: 1999 AN: 5160

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4824

European-Finnish (FIN) AF: 0.344 AC: 3637 AN: 10568

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.367 AC: 24916 AN: 67954

Other (OTH) AF: 0.371 AC: 783 AN: 2110

Alfa AF: 0.367 Hom.: 13439

Bravo AF: 0.350

Asia WGS AF: 0.416 AC: 1443 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		1.5
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: rs2864873; hg19: chr1-150814174;