Genetic Variant ANTXR1:c.952-21G>A (chr2-69152148-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.84

Publications

1 publications found

Variant links:

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]

ANTXR1 Gene-Disease associations (from GenCC):

GAPO syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
capillary infantile hemangioma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANTXR1 links:

ENSG00000300924 (HGNC:):

ENSG00000300924 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.952-21G>A		intron	N/A	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.952-21G>A		intron	N/A	NP_444262.1	Q9H6X2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.952-21G>A	intron	N/A	ENSP00000301945.4	Q9H6X2-1
ANTXR1	ENST00000409349.7	TSL:1	c.952-21G>A	intron	N/A	ENSP00000386494.3	Q9H6X2-2
ANTXR1	ENST00000894109.1		c.952-18100G>A	intron	N/A	ENSP00000564168.1

Frequencies

GnomAD3 genomes

AF:

0.00919

AC:

1397

AN:

152074

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0142

AC:

3558

AN:

251168

AF XY:

0.0126

show subpopulations

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 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.:

AF XY:

0.00791

AC XY:

5742

AN XY:

726214

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

33438

American (AMR)

AF:

0.0212

AC:

950

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000459

AC:

AN:

26124

East Asian (EAS)

AF:

0.105

AC:

4163

AN:

39670

South Asian (SAS)

AF:

0.00240

AC:

207

AN:

86220

European-Finnish (FIN)

AF:

0.0112

AC:

591

AN:

52988

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00494

AC:

5489

AN:

1110238

Other (OTH)

AF:

0.00787

AC:

475

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

615

1231

1846

2462

3077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00916

AC:

1394

AN:

152192

Hom.:

Cov.:

AF XY:

0.00969

AC XY:

721

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41516

American (AMR)

AF:

0.0174

AC:

266

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.0952

AC:

491

AN:

5160

South Asian (SAS)

AF:

0.00455

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0110

AC:

117

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00524

AC:

356

AN:

68000

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00491

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.013

(source)

DANN

Benign

0.82

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over