2-69013669-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_032208.3(ANTXR1):c.152+25dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,551,014 control chromosomes in the GnomAD database, including 96 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (46 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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 -10 ACMG points.

• BP6: Variant 2-69013669-T-TC is Benign according to our data. Variant chr2-69013669-T-TC is described in ClinVar as [Benign]. Clinvar id is 1971293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2047/151996) while in subpopulation AFR AF= 0.0455 (1888/41462). AF 95% confidence interval is 0.0438. There are 50 homozygotes in gnomad4. There are 979 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 49 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.152+25dup		intron_variant		ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.152+25dup		intron_variant		1	NM_032208.3	P1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2038 AN: 151880 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00816

GnomAD3 exomes AF: 0.00365 AC: 557 AN: 152642 Hom.: 16 AF XY: 0.00323 AC XY: 261 AN XY: 80918

Gnomad AFR exome AF: 0.0456

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.0000897

Gnomad SAS exome AF: 0.000351

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000399

Gnomad OTH exome AF: 0.00323

GnomAD4 exome AF: 0.00162 AC: 2264 AN: 1399018 Hom.: 46 Cov.: 31 AF XY: 0.00152 AC XY: 1051 AN XY: 690028

Gnomad4 AFR exome AF: 0.0463

Gnomad4 AMR exome AF: 0.00269

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.0000839

Gnomad4 SAS exome AF: 0.000215

Gnomad4 FIN exome AF: 0.0000812

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.00424

GnomAD4 genome AF: 0.0135 AC: 2047 AN: 151996 Hom.: 50 Cov.: 32 AF XY: 0.0132 AC XY: 979 AN XY: 74296

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00807

Bravo AF: 0.0147

Asia WGS AF: 0.00260 AC: 9 AN: 3478

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

Invitae

Jan 15, 2024

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Computational scores

Source: dbNSFP v4.3

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: rs200181645; hg19: chr2-69240801;