NM_032208.3:c.224+57T>C

Variant names:

• chr2-69040172-T-C
• rs13393201
• NM_032208.3:c.224+57T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032208.3(ANTXR1):​c.224+57T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,475,156 control chromosomes in the GnomAD database, including 367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (219 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (148 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• capillary infantile hemangioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-69040172-T-C is Benign according to our data. Variant chr2-69040172-T-C is described in ClinVar as Benign. ClinVar VariationId is 1236051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0927 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	NM_032208.3	MANE Select	c.224+57T>C		intron	N/A	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.224+57T>C		intron	N/A	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.224+57T>C		intron	N/A	NP_001397769.1	H0YC24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.224+57T>C		intron	N/A	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000409349.7	TSL:1	c.224+57T>C		intron	N/A	ENSP00000386494.3	Q9H6X2-2
	ANTXR1	ENST00000409829.7	TSL:1	c.224+57T>C		intron	N/A	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4158 AN: 152162 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00268 AC: 3541 AN: 1322876 Hom.: 148 AF XY: 0.00227 AC XY: 1508 AN XY: 665394

African (AFR) AF: 0.0961 AC: 2924 AN: 30436

American (AMR) AF: 0.00377 AC: 166 AN: 44018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24982

East Asian (EAS) AF: 0.00 AC: 0 AN: 38370

South Asian (SAS) AF: 0.000279 AC: 23 AN: 82540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52624

Middle Eastern (MID) AF: 0.00309 AC: 17 AN: 5496

European-Non Finnish (NFE) AF: 0.000113 AC: 112 AN: 989066

Other (OTH) AF: 0.00540 AC: 299 AN: 55344

GnomAD4 genome AF: 0.0273 AC: 4164 AN: 152280 Hom.: 219 Cov.: 32 AF XY: 0.0260 AC XY: 1936 AN XY: 74464

African (AFR) AF: 0.0951 AC: 3953 AN: 41552

American (AMR) AF: 0.00967 AC: 148 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68008

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.00869 Hom.: 73

Bravo AF: 0.0313

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.38
PhyloP100		-1.2
PromoterAI		0.0092	Neutral
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: rs13393201; hg19: chr2-69267304;