rs2228099

chr1-150836413-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001668.4(ARNT):c.567G>C(p.Val189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,580 control chromosomes in the GnomAD database, including 124,120 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 (13711 hom., cov: 32)
  • Exomes 𝑓: 0.38 (110409 hom.)
• Consequence: ARNT NM_001668.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.305 with no splicing effect.
• 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	UniProt
ARNT	NM_001668.4	c.567G>C	p.Val189=	synonymous_variant	7/22	ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.567G>C	p.Val189=	synonymous_variant	7/22	1	NM_001668.4	P3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63496 AN: 151856 Hom.: 13700 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.413

GnomAD3 exomes AF: 0.407 AC: 101998 AN: 250672 Hom.: 21351 AF XY: 0.412 AC XY: 55810 AN XY: 135534

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.465

Gnomad EAS exome AF: 0.368

Gnomad SAS exome AF: 0.536

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.396

GnomAD4 exome AF: 0.385 AC: 562627 AN: 1461606 Hom.: 110409 Cov.: 47 AF XY: 0.389 AC XY: 282972 AN XY: 727100

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.418 AC: 63534 AN: 151974 Hom.: 13711 Cov.: 32 AF XY: 0.421 AC XY: 31294 AN XY: 74276

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.416

Alfa AF: 0.387 Hom.: 4027

Bravo AF: 0.422

Asia WGS AF: 0.428 AC: 1486 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	6.2
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2228099; hg19: chr1-150808889; COSMIC: COSV62229502; COSMIC: COSV62229502;