chr2-69181897-C-A

Variant names:

• chr2-69181897-C-A
• rs6749826
• NM_032208.3:c.1185+16C>A

Variant summary

Our verdict is Benign. The variant received -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:6
• Conservation: PhyloP100: -0.406
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 262019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	NM_032208.3	MANE Select	c.1185+16C>A		intron	N/A	NP_115584.1	Q9H6X2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.1185+16C>A		intron	N/A	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000894109.1		c.1089+16C>A		intron	N/A	ENSP00000564168.1
	RNA5SP96	ENST00000516041.1	TSL:6	n.107G>T		splice_region non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.481 AC: 120775 AN: 251062 AF XY: 0.487

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 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

African (AFR) AF: 0.518 AC: 17337 AN: 33442

American (AMR) AF: 0.473 AC: 21157 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 11039 AN: 26116

East Asian (EAS) AF: 0.781 AC: 30988 AN: 39688

South Asian (SAS) AF: 0.658 AC: 56701 AN: 86186

European-Finnish (FIN) AF: 0.302 AC: 16092 AN: 53370

Middle Eastern (MID) AF: 0.559 AC: 3220 AN: 5762

European-Non Finnish (NFE) AF: 0.432 AC: 479878 AN: 1110460

Other (OTH) AF: 0.478 AC: 28851 AN: 60320

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

African (AFR) AF: 0.508 AC: 21031 AN: 41380

American (AMR) AF: 0.487 AC: 7424 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3464

East Asian (EAS) AF: 0.767 AC: 3958 AN: 5158

South Asian (SAS) AF: 0.672 AC: 3227 AN: 4800

European-Finnish (FIN) AF: 0.296 AC: 3134 AN: 10580

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29169 AN: 67940

Other (OTH) AF: 0.480 AC: 1009 AN: 2104

Alfa AF: 0.452 Hom.: 4610

Bravo AF: 0.481

Asia WGS AF: 0.647 AC: 2251 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Capillary infantile hemangioma (1)
-	-	1	GAPO syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6749826; hg19: chr2-69409029;