1-150810982-C-T

Variant names:

• chr1-150810982-C-T
• rs10305751
• NM_001668.4:c.*1039G>A

Variant summary

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

The NM_001668.4(ARNT):​c.*1039G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 229,814 control chromosomes in the GnomAD database, including 407 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 0.046 (375 hom., cov: 32)
  • Exomes 𝑓: 0.019 (32 hom.)
• Consequence: ARNT NM_001668.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.*1039G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595	c.*1039G>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000354396	c.*1039G>A		3_prime_UTR_variant	Exon 22 of 22	1		ENSP00000346372.2
ARNT	ENST00000471844.6	n.*1426G>A		non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000425899.1
ARNT	ENST00000471844.6	n.*1426G>A		3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6936 AN: 152120 Hom.: 377 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0193 AC: 1500 AN: 77576 Hom.: 32 Cov.: 0 AF XY: 0.0178 AC XY: 638 AN XY: 35768

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.0372

Gnomad4 EAS exome AF: 0.0000906

Gnomad4 SAS exome AF: 0.00455

Gnomad4 FIN exome AF: 0.00435

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0456 AC: 6939 AN: 152238 Hom.: 375 Cov.: 32 AF XY: 0.0444 AC XY: 3308 AN XY: 74452

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0169 Hom.: 96

Bravo AF: 0.0523

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.5
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: rs10305751; hg19: chr1-150783458;