NM_032208.3:c.-294G>A

Variant names:

• chr2-69013206-G-A
• rs13390810
• NM_032208.3:c.-294G>A

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.-294G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 471,478 control chromosomes in the GnomAD database, including 384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (312 hom., cov: 31)
  • Exomes 𝑓: 0.0049 (72 hom.)
• Consequence: ANTXR1 NM_032208.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.256
• Publications: 1 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

ENSG00000300948 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-69013206-G-A is Benign according to our data. Variant chr2-69013206-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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.-294G>A		5_prime_UTR	Exon 1 of 18	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.-294G>A		5_prime_UTR	Exon 1 of 15	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.-294G>A		5_prime_UTR	Exon 1 of 13	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.-294G>A		5_prime_UTR	Exon 1 of 18	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000481119.2	TSL:3	n.31G>A		non_coding_transcript_exon	Exon 1 of 8
	ENSG00000300948	ENST00000775215.1		n.111C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5061 AN: 145446 Hom.: 310 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000429

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000506

Gnomad OTH AF: 0.0251

GnomAD4 exome AF: 0.00486 AC: 1585 AN: 325940 Hom.: 72 Cov.: 0 AF XY: 0.00402 AC XY: 686 AN XY: 170806

African (AFR) AF: 0.129 AC: 1190 AN: 9212

American (AMR) AF: 0.00813 AC: 113 AN: 13898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9904

East Asian (EAS) AF: 0.00 AC: 0 AN: 24032

South Asian (SAS) AF: 0.000371 AC: 12 AN: 32320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21248

Middle Eastern (MID) AF: 0.00208 AC: 3 AN: 1442

European-Non Finnish (NFE) AF: 0.000308 AC: 60 AN: 194578

Other (OTH) AF: 0.0107 AC: 207 AN: 19306

GnomAD4 genome AF: 0.0349 AC: 5081 AN: 145538 Hom.: 312 Cov.: 31 AF XY: 0.0337 AC XY: 2369 AN XY: 70314

African (AFR) AF: 0.123 AC: 4806 AN: 39188

American (AMR) AF: 0.0138 AC: 191 AN: 13878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 4878

South Asian (SAS) AF: 0.00 AC: 0 AN: 4658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.000506 AC: 34 AN: 67138

Other (OTH) AF: 0.0249 AC: 50 AN: 2012

Alfa AF: 0.0207 Hom.: 77

Bravo AF: 0.0387

Asia WGS AF: 0.00751 AC: 26 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	-0.75
CADD	Benign	10
DANN	Benign	0.93
PhyloP100		-0.26
PromoterAI		0.014	Neutral
Mutation Taster		=294/6	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: rs13390810; hg19: chr2-69240338;