rs3768016

chr1-150837443-T-Cchr1-150837443-T-G

Variant summary

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

The NM_001668.4(ARNT):c.487-950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,020 control chromosomes in the GnomAD database, including 9,442 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 (9442 hom., cov: 31)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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=-0.83).
• 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/exons	MANE	UniProt
ARNT	NM_001668.4	c.487-950A>G		intron_variant		ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.487-950A>G		intron_variant		1	NM_001668.4	P3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52602 AN: 151902 Hom.: 9434 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.346 AC: 52626 AN: 152020 Hom.: 9442 Cov.: 31 AF XY: 0.352 AC XY: 26127 AN XY: 74300

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.359

Alfa AF: 0.359 Hom.: 9465

Bravo AF: 0.341

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	-0.83
Cadd	Benign	6.5
Dann	Benign	0.73

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: rs3768016; hg19: chr1-150809919;