2-69081064-T-C

Variant names:

• chr2-69081064-T-C
• rs12713670
• NM_032208.3:c.642+3576T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032208.3(ANTXR1):​c.642+3576T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,026 control chromosomes in the GnomAD database, including 40,112 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 0.72 (40112 hom., cov: 31)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR1	NM_032208.3	c.642+3576T>C		intron_variant	Intron 8 of 17	ENST00000303714.9	NP_115584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9	c.642+3576T>C		intron_variant	Intron 8 of 17	1	NM_032208.3	ENSP00000301945.4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109358 AN: 151908 Hom.: 40071 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.720 AC: 109462 AN: 152026 Hom.: 40112 Cov.: 31 AF XY: 0.718 AC XY: 53372 AN XY: 74302

African (AFR) AF: 0.847 AC: 35174 AN: 41508

American (AMR) AF: 0.789 AC: 12055 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2747 AN: 3472

East Asian (EAS) AF: 0.731 AC: 3775 AN: 5162

South Asian (SAS) AF: 0.687 AC: 3297 AN: 4802

European-Finnish (FIN) AF: 0.609 AC: 6425 AN: 10542

Middle Eastern (MID) AF: 0.748 AC: 217 AN: 290

European-Non Finnish (NFE) AF: 0.642 AC: 43639 AN: 67948

Other (OTH) AF: 0.735 AC: 1553 AN: 2112

Alfa AF: 0.667 Hom.: 79568

Bravo AF: 0.752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.40
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12713670; hg19: chr2-69308196;