2-69013519-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (51 hom., cov: 32)
  • Exomes 𝑓: 0.011 (599 hom.)
• Consequence: ANTXR1 NM_032208.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.648

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]

ACMG classification

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/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.20G>A	p.Arg7Lys	missense_variant	1/18	ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.20G>A	p.Arg7Lys	missense_variant	1/18	1	NM_032208.3	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1742 AN: 152222 Hom.: 51 Cov.: 32

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

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.: 31 AF XY: 0.0114 AC XY: 8115 AN XY: 711692

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.: 51 Cov.: 32 AF XY: 0.0148 AC XY: 1103 AN XY: 74486

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.: 69

Bravo AF: 0.00860

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000457 AC: 2

ESP6500EA AF: 0.00222 AC: 19

ExAC AF: 0.0193 AC: 2289

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

ANTXR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2020

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	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	13
Dann	Benign	0.86
DEOGEN2	Benign	0.062	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.26	T
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	T
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

Other links and lift over

dbSNP: rs28365986; hg19: chr2-69240651; COSMIC: COSV58016613;