1-150811509-T-C

Variant names:

• chr1-150811509-T-C
• rs11552229
• NM_001668.4:c.*512A>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.*512A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 233,042 control chromosomes in the GnomAD database, including 15,011 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 0.35 (9381 hom., cov: 31)
  • Exomes 𝑓: 0.37 (5630 hom.)
• Consequence: ARNT NM_001668.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 27 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 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.*512A>G		3_prime_UTR	Exon 22 of 22	NP_001659.1	P27540-1
	ARNT	NM_001350225.2		c.*512A>G		3_prime_UTR	Exon 22 of 22	NP_001337154.1
	ARNT	NM_001286036.2		c.*512A>G		3_prime_UTR	Exon 22 of 22	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.*512A>G		3_prime_UTR	Exon 22 of 22	ENSP00000351407.5	P27540-1
	ARNT	ENST00000354396.6	TSL:1	c.*512A>G		3_prime_UTR	Exon 22 of 22	ENSP00000346372.2	P27540-4
	ARNT	ENST00000471844.6	TSL:2	n.*899A>G		non_coding_transcript_exon	Exon 17 of 17	ENSP00000425899.1	A6NGV6

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52438 AN: 151550 Hom.: 9373 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.371 AC: 30170 AN: 81374 Hom.: 5630 Cov.: 0 AF XY: 0.374 AC XY: 14037 AN XY: 37526

African (AFR) AF: 0.275 AC: 1072 AN: 3894

American (AMR) AF: 0.385 AC: 966 AN: 2506

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 2210 AN: 5126

East Asian (EAS) AF: 0.390 AC: 4482 AN: 11506

South Asian (SAS) AF: 0.523 AC: 367 AN: 702

European-Finnish (FIN) AF: 0.350 AC: 128 AN: 366

Middle Eastern (MID) AF: 0.425 AC: 210 AN: 494

European-Non Finnish (NFE) AF: 0.364 AC: 18198 AN: 50018

Other (OTH) AF: 0.375 AC: 2537 AN: 6762

GnomAD4 genome AF: 0.346 AC: 52454 AN: 151668 Hom.: 9381 Cov.: 31 AF XY: 0.351 AC XY: 26062 AN XY: 74154

African (AFR) AF: 0.272 AC: 11243 AN: 41314

American (AMR) AF: 0.408 AC: 6221 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1519 AN: 3464

East Asian (EAS) AF: 0.389 AC: 1997 AN: 5138

South Asian (SAS) AF: 0.535 AC: 2568 AN: 4800

European-Finnish (FIN) AF: 0.344 AC: 3614 AN: 10520

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24178 AN: 67886

Other (OTH) AF: 0.360 AC: 759 AN: 2110

Alfa AF: 0.354 Hom.: 24130

Bravo AF: 0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.15
DANN	Benign	0.80
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11552229; hg19: chr1-150783985;