4-121669669-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001154.4(ANXA5):c.836T>C(p.Ile279Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00154 in 1,613,360 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 15 hom. )

Consequence

ANXA5
NM_001154.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.82

Publications

9 publications found

Variant links:

Genes affected

ANXA5 (HGNC:543): (annexin A5) The Annexin 5 gene spans 29 kb containing 13 exons, and encodes a single transcript of approximately 1.6 kb and a protein product with a molecular weight of about 35 kDa.The protein encoded by this gene belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth and differentiation. Annexin 5 has also been described as placental anticoagulant protein I, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4 and anchorin CII. Polymorphisms in this gene have been implicated in various obstetric complications. [provided by RefSeq, Dec 2019]

ANXA5 Gene-Disease associations (from GenCC):

pregnancy loss, recurrent, susceptibility to, 3
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ANXA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016770035).

BP6

Variant 4-121669669-A-G is Benign according to our data. Variant chr4-121669669-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3049443.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 4 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA5	NM_001154.4 link	c.836T>C	p.Ile279Thr	missense_variant	Exon 12 of 13	ENST00000296511.10	NP_001145.1	P08758V9HWE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA5	ENST00000296511.10 link	c.836T>C	p.Ile279Thr	missense_variant	Exon 12 of 13	1	NM_001154.4	ENSP00000296511.5		P08758

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

183

AN:

151810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000658

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00978

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000963

GnomAD2 exomes

AF:

0.00238

AC:

597

AN:

250952

AF XY:

0.00285

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00157

AC:

2295

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

1341

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33442

American (AMR)

AF:

0.00101

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00540

AC:

141

AN:

26122

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39676

South Asian (SAS)

AF:

0.0100

AC:

865

AN:

86236

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00728

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000962

AC:

1069

AN:

1111712

Other (OTH)

AF:

0.00179

AC:

108

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

112

224

336

448

560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

151926

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41454

American (AMR)

AF:

0.000657

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00979

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.000379

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

67974

Other (OTH)

AF:

0.000953

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00264

AC:

320

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANXA5-related disorder

Benign:1

Mar 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.;.

PhyloP100

3.8

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.066

Sift

Benign

0.058

T;D;T

Sift4G

Uncertain

0.031

D;D;D

Polyphen

0.20

B;B;P

Vest4

0.58

MVP

0.62

MPC

0.24

ClinPred

0.033

GERP RS

3.4

Varity_R

0.35

gMVP

0.57

Mutation Taster

=91/9

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

4-121669669-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over