chr1-150811509-T-C

Position:

• chr1-150811509-T-C

Variant summary

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

The NM_001668.4(ARNT):​c.*512A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 233,042 control chromosomes in the GnomAD database, including 15,011 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 (9381 hom., cov: 31)
  • Exomes 𝑓: 0.37 (5630 hom.)
• Consequence: ARNT NM_001668.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.*512A>G		3_prime_UTR_variant	22/22	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.*512A>G		3_prime_UTR_variant	22/22	1	NM_001668.4	ENSP00000351407	P3
ARNT	ENST00000354396.6	c.*512A>G		3_prime_UTR_variant	22/22	1		ENSP00000346372	A1
ARNT	ENST00000471844.6	c.*899A>G		3_prime_UTR_variant, NMD_transcript_variant	17/17	2		ENSP00000425899

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52438 AN: 151550 Hom.: 9373 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.371 AC: 30170 AN: 81374 Hom.: 5630 Cov.: 0 AF XY: 0.374 AC XY: 14037 AN XY: 37526

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.346 AC: 52454 AN: 151668 Hom.: 9381 Cov.: 31 AF XY: 0.351 AC XY: 26062 AN XY: 74154

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.360

Alfa AF: 0.360 Hom.: 16415

Bravo AF: 0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.15
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11552229; hg19: chr1-150783985;