chr10-80157730-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001157.3(ANXA11):c.1369A>G(p.Ile457Val) variant causes a missense change. The variant allele was found at a frequency of 0.0117 in 1,613,916 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 19 hom., cov: 32)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

ANXA11
NM_001157.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.98

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 23
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
inclusion body myopathy and brain white matter abnormalities
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANXA11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007784903).

BP6

Variant 10-80157730-T-C is Benign according to our data. Variant chr10-80157730-T-C is described in ClinVar as Benign. ClinVar VariationId is 718544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1467 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001157.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ANXA11	NM_145868.2	MANE Select	c.1369A>G	p.Ile457Val	missense	Exon 15 of 16	NP_665875.1
ANXA11	NM_001157.3		c.1369A>G	p.Ile457Val	missense	Exon 14 of 15	NP_001148.1
ANXA11	NM_001278407.2		c.1369A>G	p.Ile457Val	missense	Exon 16 of 17	NP_001265336.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.1369A>G	p.Ile457Val	missense	Exon 15 of 16	ENSP00000404412.2
ANXA11	ENST00000372231.7	TSL:1	c.1369A>G	p.Ile457Val	missense	Exon 14 of 15	ENSP00000361305.3
ANXA11	ENST00000438331.5	TSL:1	c.1369A>G	p.Ile457Val	missense	Exon 16 of 17	ENSP00000398610.1

Frequencies

GnomAD3 genomes

AF:

0.00965

AC:

1467

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0412

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00767

GnomAD2 exomes

AF:

0.00955

AC:

2401

AN:

251286

AF XY:

0.00957

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00528

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00962

GnomAD4 exome

AF:

0.0119

AC:

17462

AN:

1461788

Hom.:

130

Cov.:

AF XY:

0.0116

AC XY:

8405

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

33480

American (AMR)

AF:

0.00380

AC:

170

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00479

AC:

125

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00139

AC:

120

AN:

86254

European-Finnish (FIN)

AF:

0.0307

AC:

1638

AN:

53412

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0132

AC:

14672

AN:

1111952

Other (OTH)

AF:

0.0111

AC:

672

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

970

1940

2910

3880

4850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.00964

AC:

1467

AN:

152128

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

775

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00217

AC:

AN:

41514

American (AMR)

AF:

0.00333

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00145

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0412

AC:

436

AN:

10592

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0125

AC:

852

AN:

67974

Other (OTH)

AF:

0.00759

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

148

221

295

369

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:

0.0103

Hom.:

Bravo

AF:

0.00704

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00894

AC:

1086

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.00978

ClinVar

ClinVar submissions as Germline

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

0.042

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.53

PhyloP100

5.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.37

REVEL

Benign

0.099

Sift

Benign

0.20

Sift4G

Benign

0.38

Polyphen

0.41

Vest4

0.15

MVP

0.20

MPC

0.14

ClinPred

0.014

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.32

Mutation Taster

=100/0

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

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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