2-69081064-T-C

Position:

• chr2-69081064-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
ANTXR1	NM_032208.3	c.642+3576T>C		intron_variant		ENST00000303714.9	NP_115584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9	c.642+3576T>C		intron_variant		1	NM_032208.3	ENSP00000301945	P1

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

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.735

Alfa AF: 0.660 Hom.: 52476

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

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: rs12713670; hg19: chr2-69308196;