rs139807657

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032208.3(ANTXR1):c.1553C>T(p.Ala518Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,538,722 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A518A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 18)

Exomes 𝑓: 0.00044 ( 2 hom. )

Consequence

ANTXR1
NM_032208.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.72

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

GAPO syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
capillary infantile hemangioma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANTXR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045113564).

BP6

Variant 2-69245343-C-T is Benign according to our data. Variant chr2-69245343-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 445474.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR1	NM_032208.3 link	c.1553C>T	p.Ala518Val	missense_variant	Exon 18 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.1553C>T	p.Ala518Val	missense_variant	Exon 18 of 18	1	NM_032208.3	ENSP00000301945.4		Q9H6X2-1

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

325

AN:

137130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00824

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000187

Gnomad OTH

AF:

0.00109

GnomAD2 exomes

AF:

0.00106

AC:

203

AN:

192360

AF XY:

0.000832

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.000494

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000208

Gnomad FIN exome

AF:

0.0000566

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000435

AC:

610

AN:

1401510

Hom.:

Cov.:

AF XY:

0.000379

AC XY:

263

AN XY:

694250

show subpopulations

African (AFR)

AF:

0.0113

AC:

358

AN:

31804

American (AMR)

AF:

0.000594

AC:

AN:

38734

Ashkenazi Jewish (ASJ)

AF:

0.0000420

AC:

AN:

23828

East Asian (EAS)

AF:

0.000110

AC:

AN:

36278

South Asian (SAS)

AF:

0.0000368

AC:

AN:

81446

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

48484

Middle Eastern (MID)

AF:

0.00162

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.000128

AC:

138

AN:

1078162

Other (OTH)

AF:

0.00112

AC:

AN:

57216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00245

AC:

336

AN:

137212

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

147

AN XY:

66188

show subpopulations

African (AFR)

AF:

0.00853

AC:

307

AN:

36002

American (AMR)

AF:

0.00112

AC:

AN:

13422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3332

East Asian (EAS)

AF:

0.00

AC:

AN:

4454

South Asian (SAS)

AF:

0.00

AC:

AN:

3852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000187

AC:

AN:

64022

Other (OTH)

AF:

0.00108

AC:

AN:

1858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00170

Hom.:

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00119

AC:

140

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 518 of the ANTXR1 protein (p.Ala518Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ANTXR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 445474). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

May 08, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Capillary infantile hemangioma

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.035

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

1.7

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.47

REVEL

Benign

0.059

Sift

Benign

0.28

Sift4G

Benign

0.27

Polyphen

0.96

Vest4

0.28

MVP

0.40

MPC

0.17

ClinPred

0.011

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over