rs1802932

chr10-80157730-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_145868.2(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. 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.

• Frequency:
  • Genomes: 𝑓 0.0096 (19 hom., cov: 32)
  • Exomes 𝑓: 0.012 (130 hom.)
• Consequence: ANXA11 NM_145868.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.98

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]

ACMG classification

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 GnomAd at 1467 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA11	NM_145868.2	c.1369A>G	p.Ile457Val	missense_variant	15/16	ENST00000422982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA11	ENST00000422982.8	c.1369A>G	p.Ile457Val	missense_variant	15/16	1	NM_145868.2	P2

Frequencies

GnomAD3 genomes AF: 0.00965 AC: 1467 AN: 152010 Hom.: 19 Cov.: 32

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

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

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

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ANXA11: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 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
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

Other links and lift over

dbSNP: rs1802932; hg19: chr10-81917486;