rs3215133

Variant names:

• chr1-150829796-AT-A
• rs3215133
• NM_001668.4:c.1032+107delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001668.4(ARNT):​c.1032+107delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 1,210,486 control chromosomes in the GnomAD database, including 6,760 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.081 (750 hom., cov: 31)
  • Exomes 𝑓: 0.097 (6010 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001668.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	NM_001668.4	MANE Select	c.1032+107delA		intron	N/A	NP_001659.1
	ARNT	NM_001350225.2		c.1029+107delA		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.1032+107delA		intron	N/A	NP_001272965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	ENST00000358595.10	TSL:1 MANE Select	c.1032+107delA		intron	N/A	ENSP00000351407.5
	ARNT	ENST00000354396.6	TSL:1	c.1032+107delA		intron	N/A	ENSP00000346372.2
	ARNT	ENST00000515192.5	TSL:1	c.990+107delA		intron	N/A	ENSP00000423851.1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12359 AN: 152162 Hom.: 747 Cov.: 31

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0662

GnomAD4 exome AF: 0.0974 AC: 103032 AN: 1058206 Hom.: 6010 AF XY: 0.0946 AC XY: 50470 AN XY: 533544

African (AFR) AF: 0.0169 AC: 418 AN: 24754

American (AMR) AF: 0.183 AC: 5681 AN: 30972

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 785 AN: 20954

East Asian (EAS) AF: 0.00910 AC: 331 AN: 36370

South Asian (SAS) AF: 0.0337 AC: 2294 AN: 68112

European-Finnish (FIN) AF: 0.166 AC: 7254 AN: 43582

Middle Eastern (MID) AF: 0.0176 AC: 86 AN: 4882

European-Non Finnish (NFE) AF: 0.105 AC: 82278 AN: 782076

Other (OTH) AF: 0.0840 AC: 3905 AN: 46504

GnomAD4 genome AF: 0.0812 AC: 12363 AN: 152280 Hom.: 750 Cov.: 31 AF XY: 0.0852 AC XY: 6343 AN XY: 74438

African (AFR) AF: 0.0202 AC: 839 AN: 41584

American (AMR) AF: 0.148 AC: 2262 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3472

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5186

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4830

European-Finnish (FIN) AF: 0.167 AC: 1774 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6985 AN: 68014

Other (OTH) AF: 0.0655 AC: 138 AN: 2108

Alfa AF: 0.0384 Hom.: 42

Bravo AF: 0.0781

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
Mutation Taster		=97/3	polymorphism

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: rs3215133; hg19: chr1-150802272; COSMIC: COSV62231061;