rs4527236

Variant names:

• chr2-69040196-A-G
• rs4527236
• NM_032208.3:c.224+81A>G

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+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,253,810 control chromosomes in the GnomAD database, including 2,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (189 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1858 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.124
• 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: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BP6: Variant 2-69040196-A-G is Benign according to our data. Variant chr2-69040196-A-G is described in ClinVar as Benign. ClinVar VariationId is 1226791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0621 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+81A>G		intron	N/A	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.224+81A>G		intron	N/A	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.224+81A>G		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+81A>G		intron	N/A	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000409349.7	TSL:1	c.224+81A>G		intron	N/A	ENSP00000386494.3	Q9H6X2-2
	ANTXR1	ENST00000409829.7	TSL:1	c.224+81A>G		intron	N/A	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6658 AN: 152198 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.0537 AC: 59129 AN: 1101494 Hom.: 1858 AF XY: 0.0532 AC XY: 29858 AN XY: 561372

African (AFR) AF: 0.0146 AC: 377 AN: 25796

American (AMR) AF: 0.0417 AC: 1736 AN: 41588

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 1234 AN: 23138

East Asian (EAS) AF: 0.000112 AC: 4 AN: 35632

South Asian (SAS) AF: 0.0212 AC: 1618 AN: 76296

European-Finnish (FIN) AF: 0.0391 AC: 1987 AN: 50756

Middle Eastern (MID) AF: 0.0591 AC: 292 AN: 4944

European-Non Finnish (NFE) AF: 0.0621 AC: 49444 AN: 795720

Other (OTH) AF: 0.0512 AC: 2437 AN: 47624

GnomAD4 genome AF: 0.0437 AC: 6659 AN: 152316 Hom.: 189 Cov.: 32 AF XY: 0.0417 AC XY: 3104 AN XY: 74470

African (AFR) AF: 0.0134 AC: 559 AN: 41572

American (AMR) AF: 0.0564 AC: 863 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4824

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4332 AN: 68030

Other (OTH) AF: 0.0553 AC: 117 AN: 2116

Alfa AF: 0.0569 Hom.: 76

Bravo AF: 0.0451

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	GAPO syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		-0.12
PromoterAI		0.037	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: rs4527236; hg19: chr2-69267328;