chr1-150837443-T-C

Variant names:

• chr1-150837443-T-C
• rs3768016
• NM_001668.4:c.487-950A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001668.4(ARNT):​c.487-950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,020 control chromosomes in the GnomAD database, including 9,442 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 0.35 (9442 hom., cov: 31)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.487-950A>G		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.487-950A>G		intron_variant	Intron 6 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.487-950A>G		intron_variant	Intron 6 of 16	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52602 AN: 151902 Hom.: 9434 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.346 AC: 52626 AN: 152020 Hom.: 9442 Cov.: 31 AF XY: 0.352 AC XY: 26127 AN XY: 74300

African (AFR) AF: 0.274 AC: 11373 AN: 41464

American (AMR) AF: 0.409 AC: 6242 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3472

East Asian (EAS) AF: 0.386 AC: 1989 AN: 5150

South Asian (SAS) AF: 0.533 AC: 2565 AN: 4812

European-Finnish (FIN) AF: 0.342 AC: 3614 AN: 10572

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24191 AN: 67964

Other (OTH) AF: 0.359 AC: 757 AN: 2108

Alfa AF: 0.355 Hom.: 12224

Bravo AF: 0.341

Asia WGS AF: 0.412 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3768016; hg19: chr1-150809919;