chr2-69013519-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032208.3(ANTXR1):c.20G>A(p.Arg7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,588,742 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.011 ( 51 hom., cov: 32)

Exomes 𝑓: 0.011 ( 599 hom. )

Consequence

ANTXR1
NM_032208.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.648

Variant links:

Genes affected

ANTXR1 (HGNC:21014): (ANTXR cell adhesion molecule 1) This gene encodes a type I transmembrane protein and is a tumor-specific endothelial marker that has been implicated in colorectal cancer. The encoded protein has been shown to also be a docking protein or receptor for Bacillus anthracis toxin, the causative agent of the disease, anthrax. The binding of the protective antigen (PA) component, of the tripartite anthrax toxin, to this receptor protein mediates delivery of toxin components to the cytosol of cells. Once inside the cell, the other two components of anthrax toxin, edema factor (EF) and lethal factor (LF) disrupt normal cellular processes. Three alternatively spliced variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

ANTXR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014003515).

BP6

Variant 2-69013519-G-A is Benign according to our data. Variant chr2-69013519-G-A is described in ClinVar as [Benign]. Clinvar id is 1180103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69013519-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR1	NM_032208.3 link	c.20G>A	p.Arg7Lys	missense_variant	Exon 1 of 18	ENST00000303714.9	NP_115584.1	Q9H6X2-1Q53FL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9 link	c.20G>A	p.Arg7Lys	missense_variant	Exon 1 of 18	1	NM_032208.3	ENSP00000301945.4		Q9H6X2-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1742

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0501

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.0245

AC:

5024

AN:

205318

Hom.:

191

AF XY:

0.0242

AC XY:

2666

AN XY:

110204

show subpopulations

Gnomad AFR exome

AF:

0.000558

Gnomad AMR exome

AF:

0.0256

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.0497

Gnomad FIN exome

AF:

0.0447

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0106

AC:

15160

AN:

1436402

Hom.:

599

Cov.:

AF XY:

0.0114

AC XY:

8115

AN XY:

711692

show subpopulations

Gnomad4 AFR exome

AF:

0.000360

Gnomad4 AMR exome

AF:

0.0245

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.0472

Gnomad4 FIN exome

AF:

0.0424

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0114

AC:

1744

AN:

152340

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1103

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.0501

Gnomad4 FIN

AF:

0.0461

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00785

Hom.:

Bravo

AF:

0.00860

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00222

AC:

ExAC

AF:

0.0193

AC:

2289

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 09, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ANTXR1-related disorder

Benign:1

Feb 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.062

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.39

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.022

MPC

0.90

ClinPred

0.0029

GERP RS

-2.8

Varity_R

0.046

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over