10-80163449-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145868.2(ANXA11):c.1030-44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,612,832 control chromosomes in the GnomAD database, including 93,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9469 hom., cov: 32)

Exomes 𝑓: 0.34 ( 84119 hom. )

Consequence

ANXA11
NM_145868.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.14

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-80163449-T-G is Benign according to our data. Variant chr10-80163449-T-G is described in ClinVar as Benign. ClinVar VariationId is 1252949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2 link	c.1030-44A>C		intron_variant	Intron 10 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.1030-44A>C	intron_variant	Intron 10 of 15	1	NM_145868.2	ENSP00000404412.2	P50995-1
ANXA11	ENST00000372231.7 link	c.1030-44A>C	intron_variant	Intron 9 of 14	1		ENSP00000361305.3	P50995-1
ANXA11	ENST00000438331.5 link	c.1030-44A>C	intron_variant	Intron 11 of 16	1		ENSP00000398610.1	P50995-1
ANXA11	ENST00000265447.8 link	c.931-44A>C	intron_variant	Intron 9 of 14	5		ENSP00000265447.5	P50995-2

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52768

AN:

151862

Hom.:

9440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.335

GnomAD2 exomes

AF:

0.325

AC:

81104

AN:

249498

AF XY:

0.328

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.337

AC:

491714

AN:

1460852

Hom.:

84119

Cov.:

AF XY:

0.337

AC XY:

245196

AN XY:

726652

show subpopulations

African (AFR)

AF:

0.405

AC:

13563

AN:

33468

American (AMR)

AF:

0.222

AC:

9884

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7699

AN:

26120

East Asian (EAS)

AF:

0.324

AC:

12837

AN:

39678

South Asian (SAS)

AF:

0.348

AC:

29941

AN:

86120

European-Finnish (FIN)

AF:

0.362

AC:

19334

AN:

53376

Middle Eastern (MID)

AF:

0.254

AC:

1455

AN:

5734

European-Non Finnish (NFE)

AF:

0.339

AC:

376531

AN:

1111402

Other (OTH)

AF:

0.339

AC:

20470

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

19600

39200

58800

78400

98000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12142

24284

36426

48568

60710

<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:

0.348

AC:

52844

AN:

151980

Hom.:

9469

Cov.:

AF XY:

0.346

AC XY:

25675

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.404

AC:

16750

AN:

41442

American (AMR)

AF:

0.244

AC:

3730

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1009

AN:

3468

East Asian (EAS)

AF:

0.316

AC:

1629

AN:

5150

South Asian (SAS)

AF:

0.348

AC:

1675

AN:

4816

European-Finnish (FIN)

AF:

0.372

AC:

3922

AN:

10548

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23030

AN:

67962

Other (OTH)

AF:

0.336

AC:

708

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1768

3536

5303

7071

8839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.334

Hom.:

33234

Bravo

AF:

0.342

Asia WGS

AF:

0.361

AC:

1258

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inclusion body myopathy and brain white matter abnormalities

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

(source)

DANN

Benign

0.65

PhyloP100

-2.1

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over