chr1-150839318-T-C

Variant names:

• chr1-150839318-T-C
• rs2256355
• NM_001668.4:c.486+123A>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.486+123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 882,142 control chromosomes in the GnomAD database, including 71,383 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 0.42 (13804 hom., cov: 32)
  • Exomes 𝑓: 0.39 (57579 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 23 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 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.486+123A>G		intron	N/A	NP_001659.1	P27540-1
	ARNT	NM_001350225.2		c.483+123A>G		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.486+123A>G		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.486+123A>G		intron	N/A	ENSP00000351407.5	P27540-1
	ARNT	ENST00000354396.6	TSL:1	c.486+123A>G		intron	N/A	ENSP00000346372.2	P27540-4
	ARNT	ENST00000515192.5	TSL:1	c.459+123A>G		intron	N/A	ENSP00000423851.1	P27540-3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63690 AN: 151972 Hom.: 13791 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.393 AC: 286832 AN: 730052 Hom.: 57579 AF XY: 0.398 AC XY: 149813 AN XY: 376016

African (AFR) AF: 0.513 AC: 9443 AN: 18404

American (AMR) AF: 0.431 AC: 10977 AN: 25484

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 7835 AN: 16530

East Asian (EAS) AF: 0.380 AC: 13380 AN: 35238

South Asian (SAS) AF: 0.535 AC: 29661 AN: 55468

European-Finnish (FIN) AF: 0.351 AC: 15291 AN: 43578

Middle Eastern (MID) AF: 0.453 AC: 1430 AN: 3154

European-Non Finnish (NFE) AF: 0.371 AC: 184311 AN: 496672

Other (OTH) AF: 0.408 AC: 14504 AN: 35524

GnomAD4 genome AF: 0.419 AC: 63732 AN: 152090 Hom.: 13804 Cov.: 32 AF XY: 0.422 AC XY: 31389 AN XY: 74336

African (AFR) AF: 0.501 AC: 20792 AN: 41488

American (AMR) AF: 0.442 AC: 6755 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1663 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2012 AN: 5180

South Asian (SAS) AF: 0.542 AC: 2612 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3643 AN: 10562

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24999 AN: 67982

Other (OTH) AF: 0.418 AC: 882 AN: 2112

Alfa AF: 0.401 Hom.: 2037

Bravo AF: 0.423

Asia WGS AF: 0.430 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.37
PhyloP100		-0.61
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: rs2256355; hg19: chr1-150811794; COSMIC: COSV62230099; COSMIC: COSV62230099;