dbSNP rs2573353: ANXA11:c.-57-5006G>T (chr10-80181161-C-A) – 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.-57-5006G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,196 control chromosomes in the GnomAD database, including 31,449 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 0.63 ( 31448 hom., cov: 35)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

ANXA11
NM_145868.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0540

Publications

5 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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2 link	c.-57-5006G>T		intron_variant	Intron 1 of 15	ENST00000422982.8	NP_665875.1	P50995-1Q5T0G8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8 link	c.-57-5006G>T		intron_variant	Intron 1 of 15	1	NM_145868.2	ENSP00000404412.2		P50995-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

96056

AN:

152074

Hom.:

31380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.613

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.632

AC:

96181

AN:

152192

Hom.:

31448

Cov.:

AF XY:

0.628

AC XY:

46746

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.800

AC:

33220

AN:

41534

American (AMR)

AF:

0.578

AC:

8846

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2159

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1750

AN:

5186

South Asian (SAS)

AF:

0.641

AC:

3095

AN:

4830

European-Finnish (FIN)

AF:

0.545

AC:

5759

AN:

10562

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.579

AC:

39372

AN:

67996

Other (OTH)

AF:

0.615

AC:

1301

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.627

Hom.:

5409

Bravo

AF:

0.640

Asia WGS

AF:

0.557

AC:

1939

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.7

(source)

DANN

Benign

0.73

PhyloP100

0.054

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