NM_001668.4:c.487-147G>A

Variant names:

• chr1-150836640-C-T
• rs10305695
• NM_001668.4:c.487-147G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001668.4(ARNT):​c.487-147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 777,416 control chromosomes in the GnomAD database, including 523 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 0.027 (79 hom., cov: 32)
  • Exomes 𝑓: 0.032 (444 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 9 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=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0266 (4050/152334) while in subpopulation NFE AF = 0.0412 (2801/68034). AF 95% confidence interval is 0.0399. There are 79 homozygotes in GnomAd4. There are 1846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4050 AD gene.

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.487-147G>A		intron	N/A	NP_001659.1
	ARNT	NM_001350225.2		c.484-147G>A		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.487-147G>A		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.487-147G>A		intron	N/A	ENSP00000351407.5
	ARNT	ENST00000354396.6	TSL:1	c.487-147G>A		intron	N/A	ENSP00000346372.2
	ARNT	ENST00000515192.5	TSL:1	c.460-147G>A		intron	N/A	ENSP00000423851.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4051 AN: 152216 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.00574

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0321 AC: 20059 AN: 625082 Hom.: 444 AF XY: 0.0317 AC XY: 10155 AN XY: 320292

African (AFR) AF: 0.00565 AC: 88 AN: 15572

American (AMR) AF: 0.0226 AC: 438 AN: 19384

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 1093 AN: 14754

East Asian (EAS) AF: 0.0000628 AC: 2 AN: 31832

South Asian (SAS) AF: 0.00945 AC: 443 AN: 46868

European-Finnish (FIN) AF: 0.0234 AC: 717 AN: 30676

Middle Eastern (MID) AF: 0.0389 AC: 90 AN: 2312

European-Non Finnish (NFE) AF: 0.0374 AC: 16137 AN: 431920

Other (OTH) AF: 0.0331 AC: 1051 AN: 31764

GnomAD4 genome AF: 0.0266 AC: 4050 AN: 152334 Hom.: 79 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74504

African (AFR) AF: 0.00573 AC: 238 AN: 41568

American (AMR) AF: 0.0236 AC: 361 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4830

European-Finnish (FIN) AF: 0.0194 AC: 206 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0412 AC: 2801 AN: 68034

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0398 Hom.: 164

Bravo AF: 0.0272

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		-0.13
Mutation Taster		=100/0	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: rs10305695; hg19: chr1-150809116;