rs3768017

Variant names:

• chr1-150826636-A-C
• rs3768017
• NM_001668.4:c.1168-19T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-150826636-A-C
• chr1-150826636-A-G
• chr1-150826636-A-T

Variant summary

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

The NM_001668.4(ARNT):​c.1168-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 1,569,310 control chromosomes in the GnomAD database, including 6,932 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 (587 hom., cov: 31)
  • Exomes 𝑓: 0.089 (6345 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830
• Publications: 11 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=-0.85).
• 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 rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.1168-19T>G		intron_variant	Intron 12 of 21	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.1168-19T>G		intron_variant	Intron 12 of 21	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.1168-19T>G		intron_variant	Intron 12 of 16	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11249 AN: 151938 Hom.: 584 Cov.: 31

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0746

GnomAD2 exomes AF: 0.0965 AC: 23341 AN: 241758 AF XY: 0.0996

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.0546

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.209

Gnomad FIN exome AF: 0.0923

Gnomad NFE exome AF: 0.0948

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0890 AC: 126074 AN: 1417252 Hom.: 6345 Cov.: 24 AF XY: 0.0909 AC XY: 64231 AN XY: 706768

African (AFR) AF: 0.0117 AC: 377 AN: 32218

American (AMR) AF: 0.0562 AC: 2441 AN: 43408

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3880 AN: 25612

East Asian (EAS) AF: 0.183 AC: 7224 AN: 39374

South Asian (SAS) AF: 0.106 AC: 8878 AN: 83812

European-Finnish (FIN) AF: 0.0954 AC: 5040 AN: 52856

Middle Eastern (MID) AF: 0.125 AC: 628 AN: 5032

European-Non Finnish (NFE) AF: 0.0858 AC: 92368 AN: 1076226

Other (OTH) AF: 0.0892 AC: 5238 AN: 58714

GnomAD4 genome AF: 0.0741 AC: 11261 AN: 152058 Hom.: 587 Cov.: 31 AF XY: 0.0745 AC XY: 5536 AN XY: 74344

African (AFR) AF: 0.0140 AC: 583 AN: 41512

American (AMR) AF: 0.0671 AC: 1025 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.184 AC: 949 AN: 5156

South Asian (SAS) AF: 0.103 AC: 496 AN: 4818

European-Finnish (FIN) AF: 0.0959 AC: 1013 AN: 10558

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6380 AN: 67958

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0950 Hom.: 315

Bravo AF: 0.0718

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.54
PhyloP100		0.83
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: rs3768017; hg19: chr1-150799112; COSMIC: COSV62229819;