1-150876205-G-C

Variant names:

• chr1-150876205-G-C
• rs3820541
• NM_001668.4:c.25+338C>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.25+338C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,218 control chromosomes in the GnomAD database, including 585 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 0.074 (585 hom., cov: 32)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 8 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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	NM_001668.4	MANE Select	c.25+338C>G		intron	N/A	NP_001659.1
	ARNT	NM_001350225.2		c.-13+338C>G		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.25+338C>G		intron	N/A	NP_001272965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	ENST00000358595.10	TSL:1 MANE Select	c.25+338C>G		intron	N/A	ENSP00000351407.5
	ARNT	ENST00000354396.6	TSL:1	c.25+338C>G		intron	N/A	ENSP00000346372.2
	ARNT	ENST00000515192.5	TSL:1	c.-59+338C>G		intron	N/A	ENSP00000423851.1

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11218 AN: 152100 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0738 AC: 11230 AN: 152218 Hom.: 585 Cov.: 32 AF XY: 0.0743 AC XY: 5527 AN XY: 74424

African (AFR) AF: 0.0140 AC: 582 AN: 41558

American (AMR) AF: 0.0674 AC: 1030 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3472

East Asian (EAS) AF: 0.184 AC: 950 AN: 5164

South Asian (SAS) AF: 0.103 AC: 496 AN: 4806

European-Finnish (FIN) AF: 0.0964 AC: 1021 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6331 AN: 68018

Other (OTH) AF: 0.0771 AC: 163 AN: 2114

Alfa AF: 0.0441 Hom.: 40

Bravo AF: 0.0714

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		0.25
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3820541; hg19: chr1-150848681;