2-69013211-G-T

Variant names:

• chr2-69013211-G-T
• rs13390812
• NM_032208.3:c.-289G>T

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.-289G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 463,266 control chromosomes in the GnomAD database, including 394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (315 hom., cov: 31)
  • Exomes 𝑓: 0.0052 (79 hom.)
• Consequence: ANTXR1 NM_032208.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.194
• 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=-0.54).
• BP6: Variant 2-69013211-G-T is Benign according to our data. Variant chr2-69013211-G-T is described in ClinVar as Benign. ClinVar VariationId is 1225718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 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.-289G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_032208.3	MANE Select	c.-289G>T		5_prime_UTR	Exon 1 of 18	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.-289G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_444262.1	Q9H6X2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.-289G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.-289G>T		5_prime_UTR	Exon 1 of 18	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000481119.2	TSL:3	n.36G>T		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5112 AN: 146066 Hom.: 313 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000434

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000505

Gnomad OTH AF: 0.0243

GnomAD4 exome AF: 0.00523 AC: 1658 AN: 317108 Hom.: 79 Cov.: 3 AF XY: 0.00428 AC XY: 714 AN XY: 166696

African (AFR) AF: 0.140 AC: 1246 AN: 8922

American (AMR) AF: 0.00904 AC: 118 AN: 13056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9534

East Asian (EAS) AF: 0.00 AC: 0 AN: 20578

South Asian (SAS) AF: 0.000353 AC: 12 AN: 33984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20430

Middle Eastern (MID) AF: 0.00216 AC: 3 AN: 1388

European-Non Finnish (NFE) AF: 0.000330 AC: 63 AN: 190768

Other (OTH) AF: 0.0117 AC: 216 AN: 18448

GnomAD4 genome AF: 0.0351 AC: 5133 AN: 146158 Hom.: 315 Cov.: 31 AF XY: 0.0338 AC XY: 2393 AN XY: 70850

African (AFR) AF: 0.123 AC: 4857 AN: 39334

American (AMR) AF: 0.0137 AC: 193 AN: 14060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4754

South Asian (SAS) AF: 0.00 AC: 0 AN: 4596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.000505 AC: 34 AN: 67280

Other (OTH) AF: 0.0240 AC: 49 AN: 2042

Alfa AF: 0.0295 Hom.: 22

Bravo AF: 0.0388

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	-0.54
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.19
PromoterAI		-0.043	Neutral
Mutation Taster		=300/0	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: rs13390812; hg19: chr2-69240343;