rs10305695

Variant names:

• chr1-150836640-C-T
• rs10305695
• NM_001668.4:c.487-147G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001668.4(ARNT):​c.487-147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 777,416 control chromosomes in the GnomAD database, including 523 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 0.027 (79 hom., cov: 32)
  • Exomes 𝑓: 0.032 (444 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0266 (4050/152334) while in subpopulation NFE AF= 0.0412 (2801/68034). AF 95% confidence interval is 0.0399. There are 79 homozygotes in gnomad4. There are 1846 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4050 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.487-147G>A		intron_variant	Intron 6 of 21	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.487-147G>A		intron_variant	Intron 6 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.487-147G>A		intron_variant	Intron 6 of 16	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4051 AN: 152216 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.00574

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0321 AC: 20059 AN: 625082 Hom.: 444 AF XY: 0.0317 AC XY: 10155 AN XY: 320292

Gnomad4 AFR exome AF: 0.00565

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0741

Gnomad4 EAS exome AF: 0.0000628

Gnomad4 SAS exome AF: 0.00945

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0331

GnomAD4 genome AF: 0.0266 AC: 4050 AN: 152334 Hom.: 79 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74504

Gnomad4 AFR AF: 0.00573

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0419 Hom.: 120

Bravo AF: 0.0272

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.72

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: rs10305695; hg19: chr1-150809116;