2-69123299-T-G

Variant names:

• chr2-69123299-T-G
• rs7584948
• NM_032208.3:c.872+213T>G

Variant summary

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

The NM_032208.3(ANTXR1):​c.872+213T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,022 control chromosomes in the GnomAD database, including 7,577 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 0.28 (7577 hom., cov: 32)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 3 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

ENSG00000300924 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	NM_032208.3	MANE Select	c.872+213T>G		intron	N/A	NP_115584.1
	ANTXR1	NM_053034.2		c.872+213T>G		intron	N/A	NP_444262.1
	ANTXR1	NM_001410840.1		c.872+213T>G		intron	N/A	NP_001397769.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.872+213T>G		intron	N/A	ENSP00000301945.4
	ANTXR1	ENST00000409349.7	TSL:1	c.872+213T>G		intron	N/A	ENSP00000386494.3
	ANTXR1	ENST00000409829.7	TSL:1	c.872+213T>G		intron	N/A	ENSP00000387058.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43210 AN: 151904 Hom.: 7554 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0974

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.285 AC: 43282 AN: 152022 Hom.: 7577 Cov.: 32 AF XY: 0.280 AC XY: 20800 AN XY: 74314

African (AFR) AF: 0.495 AC: 20511 AN: 41432

American (AMR) AF: 0.269 AC: 4110 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3466

East Asian (EAS) AF: 0.0978 AC: 506 AN: 5172

South Asian (SAS) AF: 0.164 AC: 790 AN: 4812

European-Finnish (FIN) AF: 0.188 AC: 1985 AN: 10584

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14002 AN: 67968

Other (OTH) AF: 0.243 AC: 513 AN: 2112

Alfa AF: 0.223 Hom.: 17996

Bravo AF: 0.299

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		-0.17
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: rs7584948; hg19: chr2-69350431;