rs79337921

Positions:

• chr2-69152148-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032208.3(ANTXR1):​c.952-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00827 in 1,611,682 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (243 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.84

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-69152148-G-A is Benign according to our data. Variant chr2-69152148-G-A is described in ClinVar as [Benign]. Clinvar id is 1259793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANTXR1	NM_032208.3	c.952-21G>A		intron_variant		ENST00000303714.9	NP_115584.1
ANTXR1	NM_053034.2	c.952-21G>A		intron_variant			NP_444262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9	c.952-21G>A		intron_variant		1	NM_032208.3	ENSP00000301945.4
ANTXR1	ENST00000409349.7	c.952-21G>A		intron_variant		1		ENSP00000386494.3
ANTXR1	ENST00000679548.1	c.793-21G>A		intron_variant				ENSP00000505578.1

Frequencies

GnomAD3 genomes AF: 0.00919 AC: 1397 AN: 152074 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00525

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.0142 AC: 3558 AN: 251168 Hom.: 89 AF XY: 0.0126 AC XY: 1710 AN XY: 135776

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.0206

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.0969

Gnomad SAS exome AF: 0.00238

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00818 AC: 11940 AN: 1459490 Hom.: 243 Cov.: 30 AF XY: 0.00791 AC XY: 5742 AN XY: 726214

Gnomad4 AFR exome AF: 0.00126

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.00240

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.00494

Gnomad4 OTH exome AF: 0.00787

GnomAD4 genome AF: 0.00916 AC: 1394 AN: 152192 Hom.: 29 Cov.: 32 AF XY: 0.00969 AC XY: 721 AN XY: 74402

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0952

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.00524

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00491 Hom.: 2

Bravo AF: 0.0105

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.013
DANN	Benign	0.82

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: rs79337921; hg19: chr2-69379280;