rs6749826

chr2-69181897-C-Achr2-69181897-C-T

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.1185+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,611,934 control chromosomes in the GnomAD database, including 174,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17232 hom., cov: 31)
  • Exomes 𝑓: 0.46 (157174 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.406

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]

RNA5SP96 (HGNC:42894): (RNA, 5S ribosomal pseudogene 96)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-69181897-C-A is Benign according to our data. Variant chr2-69181897-C-A is described in ClinVar as [Benign]. Clinvar id is 262019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69181897-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR1	NM_032208.3	c.1185+16C>A		intron_variant		ENST00000303714.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR1	ENST00000303714.9	c.1185+16C>A		intron_variant		1	NM_032208.3	P1
RNA5SP96	ENST00000516041.1	n.107G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70909 AN: 151766 Hom.: 17228 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.484

GnomAD3 exomes AF: 0.481 AC: 120775 AN: 251062 Hom.: 30946 AF XY: 0.487 AC XY: 66096 AN XY: 135714

Gnomad AFR exome AF: 0.511

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.419

Gnomad EAS exome AF: 0.762

Gnomad SAS exome AF: 0.660

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.456 AC: 665263 AN: 1460048 Hom.: 157174 Cov.: 32 AF XY: 0.461 AC XY: 335229 AN XY: 726450

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.467 AC: 70950 AN: 151886 Hom.: 17232 Cov.: 31 AF XY: 0.467 AC XY: 34695 AN XY: 74220

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.480

Alfa AF: 0.451 Hom.: 4503

Bravo AF: 0.481

Asia WGS AF: 0.647 AC: 2251 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Capillary infantile hemangioma Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

GAPO syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.1
Dann	Benign	0.44

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: rs6749826; hg19: chr2-69409029;