rs6546473

Positions:

• chr2-69033225-A-G
• chr2-69033225-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032208.3(ANTXR1):​c.153-6819A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,074 control chromosomes in the GnomAD database, including 16,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (16312 hom., cov: 32)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANTXR1	NM_032208.3	c.153-6819A>G		intron_variant		ENST00000303714.9	NP_115584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9	c.153-6819A>G		intron_variant		1	NM_032208.3	ENSP00000301945.4

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57249 AN: 151956 Hom.: 16254 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.318

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.377 AC: 57357 AN: 152074 Hom.: 16312 Cov.: 32 AF XY: 0.380 AC XY: 28245 AN XY: 74324

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.315

Alfa AF: 0.186 Hom.: 7438

Bravo AF: 0.413

Asia WGS AF: 0.491 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.61

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: rs6546473; hg19: chr2-69260357; COSMIC: COSV100361975;