2-69040002-G-A

Position:

• chr2-69040002-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.153-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,547,994 control chromosomes in the GnomAD database, including 2,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (294 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2117 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07

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=-0.94).
• BP6: Variant 2-69040002-G-A is Benign according to our data. Variant chr2-69040002-G-A is described in ClinVar as [Benign]. Clinvar id is 1294584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.153-42G>A		intron_variant		ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.153-42G>A		intron_variant		1	NM_032208.3	P1

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8941 AN: 152152 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0602

GnomAD3 exomes AF: 0.0613 AC: 15220 AN: 248420 Hom.: 712 AF XY: 0.0558 AC XY: 7489 AN XY: 134208

Gnomad AFR exome AF: 0.0773

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.0516

Gnomad EAS exome AF: 0.0553

Gnomad SAS exome AF: 0.0363

Gnomad FIN exome AF: 0.0224

Gnomad NFE exome AF: 0.0448

Gnomad OTH exome AF: 0.0587

GnomAD4 exome AF: 0.0489 AC: 68212 AN: 1395724 Hom.: 2117 Cov.: 22 AF XY: 0.0476 AC XY: 33241 AN XY: 698170

Gnomad4 AFR exome AF: 0.0721

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.0510

Gnomad4 EAS exome AF: 0.0411

Gnomad4 SAS exome AF: 0.0354

Gnomad4 FIN exome AF: 0.0221

Gnomad4 NFE exome AF: 0.0461

Gnomad4 OTH exome AF: 0.0527

GnomAD4 genome AF: 0.0588 AC: 8946 AN: 152270 Hom.: 294 Cov.: 32 AF XY: 0.0586 AC XY: 4360 AN XY: 74464

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.0471

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0581

Alfa AF: 0.0537 Hom.: 290

Bravo AF: 0.0689

Asia WGS AF: 0.0400 AC: 138 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	-0.94
CADD	Benign	0.054
DANN	Benign	0.58

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: rs4366940; hg19: chr2-69267134;