rs1049550

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBA1

The NM_145868.2(ANXA11):c.688C>T(p.Arg230Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,605,962 control chromosomes in the GnomAD database, including 142,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R230G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.37 ( 11314 hom., cov: 32)

Exomes 𝑓: 0.42 ( 130990 hom. )

Consequence

ANXA11
NM_145868.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.63

Variant links:

Genes affected

ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

ANXA11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, BayesDel_noAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=1.5074015E-4).

BP6

Variant 10-80166946-G-A is Benign according to our data. Variant chr10-80166946-G-A is described in ClinVar as [Benign]. Clinvar id is 1297185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA11	NM_145868.2 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	7/16	ENST00000422982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA11	ENST00000422982.8 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	7/16	1	NM_145868.2	P2	P50995-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55862

AN:

151812

Hom.:

11312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.387

GnomAD3 exomes

AF:

0.420

AC:

100378

AN:

239214

Hom.:

21983

AF XY:

0.418

AC XY:

54124

AN XY:

129332

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.668

Gnomad SAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.420

AC:

610391

AN:

1454032

Hom.:

130990

Cov.:

AF XY:

0.418

AC XY:

302214

AN XY:

722822

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.651

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.422

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.368

AC:

55855

AN:

151930

Hom.:

11314

Cov.:

AF XY:

0.371

AC XY:

27546

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.378

Gnomad4 EAS

AF:

0.663

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.410

Hom.:

23699

Bravo

AF:

0.360

TwinsUK

AF:

0.427

AC:

1585

ALSPAC

AF:

0.408

AC:

1572

ESP6500AA

AF:

0.202

AC:

891

ESP6500EA

AF:

0.409

AC:

3521

ExAC

AF:

0.404

AC:

48980

Asia WGS

AF:

0.443

AC:

1538

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 21562576, 20093723, 19165924, 17000706, 24032725) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Inclusion body myopathy and brain white matter abnormalities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

T;T;.;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;.;D;D

MetaRNN

Benign

0.00015

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.7

H;H;.;H

MutationTaster

Benign

2.2e-8

P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-6.5

D;D;.;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.017

D;D;.;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.33

MPC

0.43

ClinPred

0.093

GERP RS

4.3

Varity_R

0.51

gMVP

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over