chr1-150828990-T-C

Variant names:

• chr1-150828990-T-C
• rs3738483
• NM_001668.4:c.1167+103A>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.1167+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,343,280 control chromosomes in the GnomAD database, including 539,884 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 0.84 (54422 hom., cov: 32)
  • Exomes 𝑓: 0.90 (485462 hom.)
• Consequence: ARNT NM_001668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 17 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 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.1167+103A>G		intron	N/A	NP_001659.1	P27540-1
	ARNT	NM_001350225.2		c.1164+103A>G		intron	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.1167+103A>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.1167+103A>G		intron	N/A	ENSP00000351407.5	P27540-1
	ARNT	ENST00000354396.6	TSL:1	c.1167+103A>G		intron	N/A	ENSP00000346372.2	P27540-4
	ARNT	ENST00000515192.5	TSL:1	c.1125+103A>G		intron	N/A	ENSP00000423851.1	P27540-3

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127887 AN: 152116 Hom.: 54409 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.902 AC: 1073937 AN: 1191048 Hom.: 485462 AF XY: 0.901 AC XY: 528171 AN XY: 586440

African (AFR) AF: 0.687 AC: 18344 AN: 26692

American (AMR) AF: 0.919 AC: 22782 AN: 24800

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 15978 AN: 18938

East Asian (EAS) AF: 0.816 AC: 29886 AN: 36618

South Asian (SAS) AF: 0.874 AC: 51547 AN: 59002

European-Finnish (FIN) AF: 0.904 AC: 40374 AN: 44638

Middle Eastern (MID) AF: 0.860 AC: 4257 AN: 4952

European-Non Finnish (NFE) AF: 0.915 AC: 846005 AN: 924948

Other (OTH) AF: 0.887 AC: 44764 AN: 50460

GnomAD4 genome AF: 0.840 AC: 127942 AN: 152232 Hom.: 54422 Cov.: 32 AF XY: 0.843 AC XY: 62726 AN XY: 74444

African (AFR) AF: 0.696 AC: 28895 AN: 41504

American (AMR) AF: 0.896 AC: 13712 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2954 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4186 AN: 5180

South Asian (SAS) AF: 0.873 AC: 4213 AN: 4824

European-Finnish (FIN) AF: 0.904 AC: 9585 AN: 10604

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61542 AN: 68030

Other (OTH) AF: 0.858 AC: 1811 AN: 2110

Alfa AF: 0.886 Hom.: 99573

Bravo AF: 0.831

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.74
PhyloP100		0.20
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: rs3738483; hg19: chr1-150801466;