NM_032208.3:c.296+148G>A

Variant names:

• chr2-69044961-G-A
• rs62135618
• NM_032208.3:c.296+148G>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.296+148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 735,826 control chromosomes in the GnomAD database, including 806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (141 hom., cov: 32)
  • Exomes 𝑓: 0.042 (665 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27
• 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=-0.86).
• BP6: Variant 2-69044961-G-A is Benign according to our data. Variant chr2-69044961-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0514 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.296+148G>A		intron	N/A	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.296+148G>A		intron	N/A	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.296+148G>A		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.296+148G>A		intron	N/A	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000409349.7	TSL:1	c.296+148G>A		intron	N/A	ENSP00000386494.3	Q9H6X2-2
	ANTXR1	ENST00000409829.7	TSL:1	c.296+148G>A		intron	N/A	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5156 AN: 152030 Hom.: 141 Cov.: 32

Gnomad AFR AF: 0.00858

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0419 AC: 24434 AN: 583678 Hom.: 665 AF XY: 0.0431 AC XY: 13423 AN XY: 311592

African (AFR) AF: 0.00758 AC: 119 AN: 15690

American (AMR) AF: 0.0241 AC: 779 AN: 32364

Ashkenazi Jewish (ASJ) AF: 0.0488 AC: 920 AN: 18864

East Asian (EAS) AF: 0.00125 AC: 40 AN: 31940

South Asian (SAS) AF: 0.0557 AC: 3359 AN: 60262

European-Finnish (FIN) AF: 0.0822 AC: 2958 AN: 35992

Middle Eastern (MID) AF: 0.0225 AC: 89 AN: 3952

European-Non Finnish (NFE) AF: 0.0423 AC: 14963 AN: 353538

Other (OTH) AF: 0.0388 AC: 1207 AN: 31076

GnomAD4 genome AF: 0.0339 AC: 5161 AN: 152148 Hom.: 141 Cov.: 32 AF XY: 0.0367 AC XY: 2729 AN XY: 74378

African (AFR) AF: 0.00855 AC: 355 AN: 41516

American (AMR) AF: 0.0245 AC: 374 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0569 AC: 274 AN: 4812

European-Finnish (FIN) AF: 0.0960 AC: 1015 AN: 10576

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2929 AN: 67986

Other (OTH) AF: 0.0265 AC: 56 AN: 2114

Alfa AF: 0.0388 Hom.: 21

Bravo AF: 0.0262

Asia WGS AF: 0.0260 AC: 91 AN: 3476

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	-0.86
CADD	Benign	7.1
DANN	Benign	0.59
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs62135618; hg19: chr2-69272093;