10-80157730-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_145868.2(ANXA11):ā€‹c.1369A>Gā€‹(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. Variant has been reported in ClinVar as Benign (ā˜…ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.0096 ( 19 hom., cov: 32)
Exomes š‘“: 0.012 ( 130 hom. )

Consequence

ANXA11
NM_145868.2 missense

Scores

4
14

Clinical Significance

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

Conservation

PhyloP100: 4.98
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 718544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 1467 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANXA11NM_145868.2 linkuse as main transcriptc.1369A>G p.Ile457Val missense_variant 15/16 ENST00000422982.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANXA11ENST00000422982.8 linkuse as main transcriptc.1369A>G p.Ile457Val missense_variant 15/161 NM_145868.2 P2P50995-1

Frequencies

GnomAD3 genomes
AF:
0.00965
AC:
1467
AN:
152010
Hom.:
19
Cov.:
32
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
GnomAD3 exomes
AF:
0.00955
AC:
2401
AN:
251286
Hom.:
18
AF XY:
0.00957
AC XY:
1299
AN XY:
135806
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 SAS exome
AF:
0.00121
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.:
32
AF XY:
0.0116
AC XY:
8405
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00170
Gnomad4 AMR exome
AF:
0.00380
Gnomad4 ASJ exome
AF:
0.00479
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00139
Gnomad4 FIN exome
AF:
0.0307
Gnomad4 NFE exome
AF:
0.0132
Gnomad4 OTH exome
AF:
0.0111
GnomAD4 genome
AF:
0.00964
AC:
1467
AN:
152128
Hom.:
19
Cov.:
32
AF XY:
0.0104
AC XY:
775
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00217
Gnomad4 AMR
AF:
0.00333
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.0412
Gnomad4 NFE
AF:
0.0125
Gnomad4 OTH
AF:
0.00759
Alfa
AF:
0.0108
Hom.:
14
Bravo
AF:
0.00704
TwinsUK
AF:
0.0102
AC:
38
ALSPAC
AF:
0.0145
AC:
56
ESP6500AA
AF:
0.00295
AC:
13
ESP6500EA
AF:
0.0122
AC:
105
ExAC
AF:
0.00894
AC:
1086
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0117
EpiControl
AF:
0.00978

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024ANXA11: BS1, BS2 -
Benign, criteria provided, single submitterclinical testingInvitaeJan 28, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T;T;.;T
Eigen
Benign
0.042
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.87
.;.;D;D
MetaRNN
Benign
0.0078
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.53
N;N;.;N
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.37
N;N;.;N
REVEL
Benign
0.099
Sift
Benign
0.20
T;T;.;T
Sift4G
Benign
0.38
T;T;T;T
Polyphen
0.41
B;B;.;B
Vest4
0.15
MVP
0.20
MPC
0.14
ClinPred
0.014
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.32

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.

Other links and lift over

dbSNP: rs1802932; hg19: chr10-81917486; API