2-69040196-A-G

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.224+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,253,810 control chromosomes in the GnomAD database, including 2,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (189 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1858 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.124

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 (BayesDel_noAF=-0.88).
• BP6: Variant 2-69040196-A-G is Benign according to our data. Variant chr2-69040196-A-G is described in ClinVar as [Benign]. Clinvar id is 1226791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.224+81A>G		intron_variant		ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.224+81A>G		intron_variant		1	NM_032208.3	P1

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6658 AN: 152198 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.0537 AC: 59129 AN: 1101494 Hom.: 1858 AF XY: 0.0532 AC XY: 29858 AN XY: 561372

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.0417

Gnomad4 ASJ exome AF: 0.0533

Gnomad4 EAS exome AF: 0.000112

Gnomad4 SAS exome AF: 0.0212

Gnomad4 FIN exome AF: 0.0391

Gnomad4 NFE exome AF: 0.0621

Gnomad4 OTH exome AF: 0.0512

GnomAD4 genome AF: 0.0437 AC: 6659 AN: 152316 Hom.: 189 Cov.: 32 AF XY: 0.0417 AC XY: 3104 AN XY: 74470

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0532 Hom.: 31

Bravo AF: 0.0451

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GAPO syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.34

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: rs4527236; hg19: chr2-69267328;