rs10305650

Positions:

• chr1-150876501-G-A
• chr1-150876501-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000358595.10(ARNT):​c.25+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,547,072 control chromosomes in the GnomAD database, including 1,687 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 0.060 (942 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (745 hom.)
• Consequence: ARNT ENST00000358595.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.25+42C>T		intron_variant		ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.25+42C>T		intron_variant		1	NM_001668.4	ENSP00000351407	P3

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9099 AN: 152006 Hom.: 941 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.0431

GnomAD3 exomes AF: 0.0129 AC: 1922 AN: 149530 Hom.: 165 AF XY: 0.00980 AC XY: 781 AN XY: 79706

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.00915

Gnomad ASJ exome AF: 0.000121

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000792

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00624 AC: 8705 AN: 1394950 Hom.: 745 Cov.: 34 AF XY: 0.00543 AC XY: 3739 AN XY: 688152

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.000160

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000746

Gnomad4 FIN exome AF: 0.0000205

Gnomad4 NFE exome AF: 0.000679

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0599 AC: 9113 AN: 152122 Hom.: 942 Cov.: 32 AF XY: 0.0578 AC XY: 4300 AN XY: 74366

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0275 Hom.: 52

Bravo AF: 0.0689

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.93
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: rs10305650; hg19: chr1-150848977;