Genetic Variant ANXA11:c.-57-2721A>G (chr10-80178876-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145868.2(ANXA11):c.-57-2721A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,122 control chromosomes in the GnomAD database, including 1,399 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1399 hom., cov: 32)

Consequence

ANXA11
NM_145868.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2 link	c.-57-2721A>G		intron_variant	Intron 1 of 15	ENST00000422982.8	NP_665875.1	P50995-1Q5T0G8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANXA11	ENST00000422982.8 link	c.-57-2721A>G	intron_variant	Intron 1 of 15	1	NM_145868.2	ENSP00000404412.2	P50995-1
ANXA11	ENST00000372231.7 link	c.-8-6007A>G	intron_variant	Intron 1 of 14	1		ENSP00000361305.3	P50995-1
ANXA11	ENST00000438331.5 link	c.-58+2065A>G	intron_variant	Intron 2 of 16	1		ENSP00000398610.1	P50995-1
ANXA11	ENST00000463657.1 link	n.695+2065A>G	intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19573

AN:

152004

Hom.:

1393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.0920

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.129

AC:

19602

AN:

152122

Hom.:

1399

Cov.:

AF XY:

0.131

AC XY:

9706

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.104

AC:

4306

AN:

41494

American (AMR)

AF:

0.208

AC:

3182

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3472

East Asian (EAS)

AF:

0.0175

AC:

AN:

5154

South Asian (SAS)

AF:

0.240

AC:

1158

AN:

4822

European-Finnish (FIN)

AF:

0.0920

AC:

974

AN:

10588

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9089

AN:

67988

Other (OTH)

AF:

0.146

AC:

308

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

880

1759

2639

3518

4398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.143

Hom.:

282

Bravo

AF:

0.136

Asia WGS

AF:

0.147

AC:

510

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.8

(source)

DANN

Benign

0.72

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over