2-69013740-G-C

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.152+89G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,546,888 control chromosomes in the GnomAD database, including 1,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (173 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1717 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

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=-0.79).
• BP6: Variant 2-69013740-G-C is Benign according to our data. Variant chr2-69013740-G-C is described in ClinVar as [Benign]. Clinvar id is 1221510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.152+89G>C		intron_variant		ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.152+89G>C		intron_variant		1	NM_032208.3	P1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5686 AN: 152220 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0466 AC: 64957 AN: 1394550 Hom.: 1717 AF XY: 0.0466 AC XY: 32092 AN XY: 688084

Gnomad4 AFR exome AF: 0.00620

Gnomad4 AMR exome AF: 0.0683

Gnomad4 ASJ exome AF: 0.0495

Gnomad4 EAS exome AF: 0.000728

Gnomad4 SAS exome AF: 0.0518

Gnomad4 FIN exome AF: 0.0874

Gnomad4 NFE exome AF: 0.0465

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0374 AC: 5694 AN: 152338 Hom.: 173 Cov.: 32 AF XY: 0.0401 AC XY: 2989 AN XY: 74502

Gnomad4 AFR AF: 0.00856

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0407 Hom.: 23

Bravo AF: 0.0327

Asia WGS AF: 0.0240 AC: 85 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 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	17
Dann	Benign	0.69

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: rs116312139; hg19: chr2-69240872;