rs1027699

Variant names:

• chr1-150839236-T-C
• rs1027699
• NM_001668.4:c.486+205A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001668.4(ARNT):​c.486+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,080 control chromosomes in the GnomAD database, including 9,486 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 (9486 hom., cov: 32)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• 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 rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.486+205A>G		intron_variant	Intron 6 of 21	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.486+205A>G		intron_variant	Intron 6 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.486+205A>G		intron_variant	Intron 6 of 16	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52800 AN: 151964 Hom.: 9479 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.347 AC: 52814 AN: 152080 Hom.: 9486 Cov.: 32 AF XY: 0.353 AC XY: 26238 AN XY: 74342

African (AFR) AF: 0.277 AC: 11509 AN: 41484

American (AMR) AF: 0.410 AC: 6263 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2004 AN: 5170

South Asian (SAS) AF: 0.534 AC: 2573 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3612 AN: 10558

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24199 AN: 67980

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.346 Hom.: 1267

Bravo AF: 0.343

Asia WGS AF: 0.412 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.3
DANN	Benign	0.84
PhyloP100		0.047
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: rs1027699; hg19: chr1-150811712;