1-150818010-C-A

Variant names:

• chr1-150818010-C-A
• NM_001668.4:c.1415G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001668.4(ARNT):​c.1415G>T​(p.Arg472Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R472Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ARNT NM_001668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.37

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARNT	NM_001668.4	c.1415G>T	p.Arg472Leu	missense_variant	Exon 15 of 22	ENST00000358595.10	NP_001659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARNT	ENST00000358595.10	c.1415G>T	p.Arg472Leu	missense_variant	Exon 15 of 22	1	NM_001668.4	ENSP00000351407.5
ARNT	ENST00000471844.6	n.*12G>T		non_coding_transcript_exon_variant	Exon 14 of 17	2		ENSP00000425899.1
ARNT	ENST00000471844.6	n.*12G>T		3_prime_UTR_variant	Exon 14 of 17	2		ENSP00000425899.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460756 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726636

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.97	N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.023	D;D;D;D
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.075	B;.;B;B
Vest4		0.78
MutPred		0.22		Loss of phosphorylation at T474 (P = 0.0679);Loss of phosphorylation at T474 (P = 0.0679);.;.;
MVP		0.79
MPC		0.38
ClinPred		0.89	D
GERP RS		6.0
Varity_R		0.12
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150790486;