rs3768017

chr1-150826636-A-Cchr1-150826636-A-Gchr1-150826636-A-T

Variant summary

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

The NM_001668.4(ARNT):c.1168-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 1,569,310 control chromosomes in the GnomAD database, including 6,932 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 0.074 (587 hom., cov: 31)
  • Exomes 𝑓: 0.089 (6345 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT	NM_001668.4	c.1168-19T>G		intron_variant		ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.1168-19T>G		intron_variant		1	NM_001668.4	P3

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11249 AN: 151938 Hom.: 584 Cov.: 31

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0746

GnomAD3 exomes AF: 0.0965 AC: 23341 AN: 241758 Hom.: 1435 AF XY: 0.0996 AC XY: 13087 AN XY: 131402

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.0546

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.209

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.0923

Gnomad NFE exome AF: 0.0948

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0890 AC: 126074 AN: 1417252 Hom.: 6345 Cov.: 24 AF XY: 0.0909 AC XY: 64231 AN XY: 706768

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0562

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.0858

Gnomad4 OTH exome AF: 0.0892

GnomAD4 genome AF: 0.0741 AC: 11261 AN: 152058 Hom.: 587 Cov.: 31 AF XY: 0.0745 AC XY: 5536 AN XY: 74344

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0928 Hom.: 177

Bravo AF: 0.0718

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.7
Dann	Benign	0.54

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: rs3768017; hg19: chr1-150799112; COSMIC: COSV62229819; COSMIC: COSV62229819;