rs10305679

Variant names:

• chr1-150842326-A-G
• rs10305679
• NM_001668.4:c.272+98T>C

Variant summary

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

The NM_001668.4(ARNT):​c.272+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,509,356 control chromosomes in the GnomAD database, including 1,645 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 (939 hom., cov: 31)
  • Exomes 𝑓: 0.0060 (706 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 1 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 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.272+98T>C		intron	N/A	NP_001659.1	P27540-1
	ARNT	NM_001350225.2		c.269+98T>C		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.272+98T>C		intron	N/A	NP_001272965.1	P27540-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	ENST00000358595.10	TSL:1 MANE Select	c.272+98T>C		intron	N/A	ENSP00000351407.5	P27540-1
	ARNT	ENST00000354396.6	TSL:1	c.272+98T>C		intron	N/A	ENSP00000346372.2	P27540-4
	ARNT	ENST00000515192.5	TSL:1	c.245+98T>C		intron	N/A	ENSP00000423851.1	P27540-3

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9094 AN: 152122 Hom.: 939 Cov.: 31

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: 0.0253

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.00602 AC: 8175 AN: 1357116 Hom.: 706 Cov.: 30 AF XY: 0.00530 AC XY: 3557 AN XY: 671764

African (AFR) AF: 0.213 AC: 6278 AN: 29456

American (AMR) AF: 0.0116 AC: 352 AN: 30434

Ashkenazi Jewish (ASJ) AF: 0.0000906 AC: 2 AN: 22066

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36896

South Asian (SAS) AF: 0.000676 AC: 48 AN: 70962

European-Finnish (FIN) AF: 0.0000211 AC: 1 AN: 47360

Middle Eastern (MID) AF: 0.0174 AC: 91 AN: 5234

European-Non Finnish (NFE) AF: 0.000657 AC: 696 AN: 1059872

Other (OTH) AF: 0.0129 AC: 706 AN: 54836

GnomAD4 genome AF: 0.0598 AC: 9106 AN: 152240 Hom.: 939 Cov.: 31 AF XY: 0.0577 AC XY: 4297 AN XY: 74436

African (AFR) AF: 0.207 AC: 8608 AN: 41502

American (AMR) AF: 0.0212 AC: 324 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68020

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0249 Hom.: 825

Bravo AF: 0.0688

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.83
PhyloP100		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10305679; hg19: chr1-150814802;