2-69013458-G-A

Variant names:

• chr2-69013458-G-A
• rs76179551
• NM_032208.3:c.-42G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_032208.3(ANTXR1):​c.-42G>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 0.00517 in 1,578,876 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (214 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (167 hom.)
• Consequence: ANTXR1 NM_032208.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.67
• 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, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• capillary infantile hemangioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300948 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 2-69013458-G-A is Benign according to our data. Variant chr2-69013458-G-A is described in ClinVar as Benign. ClinVar VariationId is 1252458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0939 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.-42G>A		5_prime_UTR	Exon 1 of 18	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.-42G>A		5_prime_UTR	Exon 1 of 15	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.-42G>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.-42G>A		5_prime_UTR	Exon 1 of 18	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000409349.7	TSL:1	c.-42G>A		5_prime_UTR	Exon 1 of 15	ENSP00000386494.3	Q9H6X2-2
	ANTXR1	ENST00000409829.7	TSL:1	c.-42G>A		5_prime_UTR	Exon 1 of 13	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4191 AN: 152186 Hom.: 212 Cov.: 32

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00594 AC: 1137 AN: 191482 AF XY: 0.00444

Gnomad AFR exome AF: 0.0917

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00277 AC: 3956 AN: 1426572 Hom.: 167 Cov.: 31 AF XY: 0.00235 AC XY: 1658 AN XY: 705978

African (AFR) AF: 0.0982 AC: 3267 AN: 33262

American (AMR) AF: 0.00457 AC: 171 AN: 37446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25424

East Asian (EAS) AF: 0.00 AC: 0 AN: 38716

South Asian (SAS) AF: 0.000296 AC: 24 AN: 81124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50616

Middle Eastern (MID) AF: 0.00217 AC: 9 AN: 4140

European-Non Finnish (NFE) AF: 0.000120 AC: 132 AN: 1096676

Other (OTH) AF: 0.00597 AC: 353 AN: 59168

GnomAD4 genome AF: 0.0276 AC: 4209 AN: 152304 Hom.: 214 Cov.: 32 AF XY: 0.0264 AC XY: 1965 AN XY: 74498

African (AFR) AF: 0.0964 AC: 4006 AN: 41550

American (AMR) AF: 0.00948 AC: 145 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68024

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0170 Hom.: 20

Bravo AF: 0.0312

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.41
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		1.7
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs76179551; hg19: chr2-69240590;