1-150840478-G-A

Variant names:

• chr1-150840478-G-A
• rs3768015
• NM_001668.4:c.273-824C>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.273-824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,978 control chromosomes in the GnomAD database, including 9,385 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 0.34 (9385 hom., cov: 32)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.273-824C>T		intron_variant	Intron 5 of 21	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.273-824C>T		intron_variant	Intron 5 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.273-824C>T		intron_variant	Intron 5 of 16	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52409 AN: 151858 Hom.: 9377 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.345 AC: 52426 AN: 151978 Hom.: 9385 Cov.: 32 AF XY: 0.351 AC XY: 26061 AN XY: 74282

African (AFR) AF: 0.269 AC: 11150 AN: 41452

American (AMR) AF: 0.409 AC: 6253 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2002 AN: 5162

South Asian (SAS) AF: 0.534 AC: 2574 AN: 4816

European-Finnish (FIN) AF: 0.342 AC: 3603 AN: 10528

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

European-Non Finnish (NFE) AF: 0.356 AC: 24192 AN: 67956

Other (OTH) AF: 0.360 AC: 759 AN: 2108

Alfa AF: 0.350 Hom.: 1664

Bravo AF: 0.340

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.99
DANN	Benign	0.47
PhyloP100		0.046
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: rs3768015; hg19: chr1-150812954; COSMIC: COSV107438423; COSMIC: COSV107438423;