1-150876205-G-C

Position:

• chr1-150876205-G-C

Variant summary

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

The ENST00000358595.10(ARNT):​c.25+338C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,218 control chromosomes in the GnomAD database, including 585 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 0.074 (585 hom., cov: 32)
• Consequence: ARNT ENST00000358595.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARNT	NM_001668.4	c.25+338C>G		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+338C>G		intron_variant		1	NM_001668.4	ENSP00000351407	P3

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11218 AN: 152100 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0738 AC: 11230 AN: 152218 Hom.: 585 Cov.: 32 AF XY: 0.0743 AC XY: 5527 AN XY: 74424

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0964

Gnomad4 NFE AF: 0.0931

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0441 Hom.: 40

Bravo AF: 0.0714

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3820541; hg19: chr1-150848681;