1-150817408-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001668.4(ARNT):c.1531G>A(p.Asp511Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00707 in 1,614,158 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0059 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0072 (53 hom.)
• Consequence: ARNT NM_001668.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.99

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004409611).
• BP6: Variant 1-150817408-C-T is Benign according to our data. Variant chr1-150817408-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARNT	NM_001668.4	c.1531G>A	p.Asp511Asn	missense_variant	16/22	ENST00000358595.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARNT	ENST00000358595.10	c.1531G>A	p.Asp511Asn	missense_variant	16/22	1	NM_001668.4	P3

Frequencies

GnomAD3 genomes AF: 0.00590 AC: 898 AN: 152162 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.00747

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00823

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00546 AC: 1372 AN: 251470 Hom.: 6 AF XY: 0.00540 AC XY: 734 AN XY: 135908

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00114

Gnomad FIN exome AF: 0.00554

Gnomad NFE exome AF: 0.00818

Gnomad OTH exome AF: 0.00863

GnomAD4 exome AF: 0.00719 AC: 10513 AN: 1461878 Hom.: 53 Cov.: 32 AF XY: 0.00714 AC XY: 5191 AN XY: 727236

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.00570

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.00541

Gnomad4 NFE exome AF: 0.00825

Gnomad4 OTH exome AF: 0.00684

GnomAD4 genome AF: 0.00590 AC: 898 AN: 152280 Hom.: 6 Cov.: 31 AF XY: 0.00579 AC XY: 431 AN XY: 74458

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00746

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00763

Gnomad4 NFE AF: 0.00823

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00778 Hom.: 7

Bravo AF: 0.00620

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00942 AC: 81

ExAC AF: 0.00563 AC: 684

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00763

EpiControl AF: 0.00853

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	ARNT: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
MetaRNN	Benign	0.0044	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.55	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.010	D;D;D;D
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.26	B;.;B;B
Vest4		0.17
MVP		0.52
MPC		0.29
ClinPred		0.026	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.078
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs1805133; hg19: chr1-150789884;