rs7514004

Positions:

• chr1-150845758-T-C
• chr1-150845758-T-G

Variant summary

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

The ENST00000358595.10(ARNT):​c.227+505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,652 control chromosomes in the GnomAD database, including 13,762 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 0.42 (13762 hom., cov: 30)
• Consequence: ARNT ENST00000358595.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.227+505A>G		intron_variant		ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.227+505A>G		intron_variant		1	NM_001668.4	ENSP00000351407	P3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63520 AN: 151534 Hom.: 13749 Cov.: 30

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.419 AC: 63562 AN: 151652 Hom.: 13762 Cov.: 30 AF XY: 0.422 AC XY: 31289 AN XY: 74080

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.416

Alfa AF: 0.392 Hom.: 1504

Bravo AF: 0.423

Asia WGS AF: 0.430 AC: 1494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.17

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: rs7514004; hg19: chr1-150818234;