2-69044961-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1276136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.296+148G>A		intron_variant		ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.296+148G>A		intron_variant		1	NM_032208.3	P1

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

Gnomad4 AFR exome AF: 0.00758

Gnomad4 AMR exome AF: 0.0241

Gnomad4 ASJ exome AF: 0.0488

Gnomad4 EAS exome AF: 0.00125

Gnomad4 SAS exome AF: 0.0557

Gnomad4 FIN exome AF: 0.0822

Gnomad4 NFE exome AF: 0.0423

Gnomad4 OTH exome AF: 0.0388

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

Gnomad4 AFR AF: 0.00855

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0569

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0388 Hom.: 21

Bravo AF: 0.0262

Asia WGS AF: 0.0260 AC: 91 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.1
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs62135618; hg19: chr2-69272093;