chr1-150812035-G-T

Variant names:

• chr1-150812035-G-T
• rs1478022649
• NM_001668.4:c.2356C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001668.4(ARNT):​c.2356C>A​(p.Pro786Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P786A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARNT NM_001668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06648028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.2356C>A	p.Pro786Thr	missense_variant	Exon 22 of 22	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.2356C>A	p.Pro786Thr	missense_variant	Exon 22 of 22	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.*373C>A		non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000425899.1
ARNT	ENST00000471844.6	n.*373C>A		3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 225638 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T;.;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.066	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L;.;.;.
PhyloP100		0.62
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.14	N;N;N;N
REVEL	Benign	0.019
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		0.055	B;.;B;B
Vest4		0.039
MutPred		0.23		Gain of phosphorylation at P786 (P = 0.0389);.;.;.;
MVP		0.32
MPC		0.35
ClinPred		0.24	T
GERP RS		1.6
Varity_R		0.050
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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: rs1478022649; hg19: chr1-150784511;