1-150876600-C-G

Position:

• chr1-150876600-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The ENST00000515192.5(ARNT):​c.-116G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,540,072 control chromosomes in the GnomAD database, including 33 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 0.0083 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (9 hom.)
• Consequence: ARNT ENST00000515192.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

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]

ARNT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00833 (1267/152118) while in subpopulation AFR AF= 0.0294 (1221/41508). AF 95% confidence interval is 0.028. There are 24 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1267 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.-33G>C		upstream_gene_variant		ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000471844.6	n.-33G>C		non_coding_transcript_exon_variant	1/17	2		ENSP00000425899.1
ARNT	ENST00000471844.6	n.-33G>C		5_prime_UTR_variant	1/17	2		ENSP00000425899.1
ARNT	ENST00000358595.10	c.-33G>C		upstream_gene_variant		1	NM_001668.4	ENSP00000351407.5

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1263 AN: 152014 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00432

GnomAD3 exomes AF: 0.00148 AC: 208 AN: 140304 Hom.: 2 AF XY: 0.000992 AC XY: 75 AN XY: 75636

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000182

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000777

Gnomad OTH exome AF: 0.000246

GnomAD4 exome AF: 0.000807 AC: 1120 AN: 1387954 Hom.: 9 Cov.: 29 AF XY: 0.000668 AC XY: 457 AN XY: 684430

Gnomad4 AFR exome AF: 0.0305

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000186

Gnomad4 OTH exome AF: 0.00160

GnomAD4 genome AF: 0.00833 AC: 1267 AN: 152118 Hom.: 24 Cov.: 32 AF XY: 0.00766 AC XY: 570 AN XY: 74364

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.000263 Hom.: 0

Bravo AF: 0.00934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs35756904; hg19: chr1-150849076;