rs34590960

Positions:

• chr2-69152482-G-A
• chr2-69152482-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032208.3(ANTXR1):​c.1047+218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,072 control chromosomes in the GnomAD database, including 16,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16167 hom., cov: 32)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANTXR1	NM_032208.3	c.1047+218G>A		intron_variant		ENST00000303714.9	NP_115584.1
ANTXR1	NM_053034.2	c.1047+218G>A		intron_variant			NP_444262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9	c.1047+218G>A		intron_variant		1	NM_032208.3	ENSP00000301945	P1
ANTXR1	ENST00000409349.7	c.1047+218G>A		intron_variant		1		ENSP00000386494
ANTXR1	ENST00000679548.1	c.890+218G>A		intron_variant				ENSP00000505578

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68308 AN: 151954 Hom.: 16158 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68350 AN: 152072 Hom.: 16167 Cov.: 32 AF XY: 0.457 AC XY: 33941 AN XY: 74340

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.459

Alfa AF: 0.404 Hom.: 4138

Bravo AF: 0.449

Asia WGS AF: 0.691 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.60

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: rs34590960; hg19: chr2-69379614;