Genetic Variant ANXA6:c.1839+19G>A (chr5-151105226-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001155.5(ANXA6):c.1839+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 1,610,606 control chromosomes in the GnomAD database, including 7,907 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 0.12 ( 2209 hom., cov: 33)

Exomes 𝑓: 0.057 ( 5698 hom. )

Consequence

ANXA6
NM_001155.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

8 publications found

Variant links:

Genes affected

ANXA6 (HGNC:544): (annexin A6) Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths. It is highly similar to human annexins I and II sequences, each of which contain four such repeats. Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

ANXA6 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001155.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANXA6	NM_001155.5	MANE Select	c.1839+19G>A	intron	N/A	NP_001146.2	A0A0S2Z2Z6
ANXA6	NM_001363114.2		c.1821+19G>A	intron	N/A	NP_001350043.1	A0A0S2Z377
ANXA6	NM_001193544.2		c.1743+19G>A	intron	N/A	NP_001180473.1	P08133-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANXA6	ENST00000354546.10	TSL:1 MANE Select	c.1839+19G>A	intron	N/A	ENSP00000346550.5	P08133-1
ANXA6	ENST00000941434.1		c.1935+19G>A	intron	N/A	ENSP00000611493.1
ANXA6	ENST00000935749.1		c.1917+19G>A	intron	N/A	ENSP00000605808.1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18744

AN:

152086

Hom.:

2202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.0929

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.0862

AC:

21483

AN:

249164

AF XY:

0.0888

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0915

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0362

Gnomad OTH exome

AF:

0.0730

GnomAD4 exome

AF:

0.0567

AC:

82681

AN:

1458402

Hom.:

5698

Cov.:

AF XY:

0.0609

AC XY:

44184

AN XY:

725672

show subpopulations

African (AFR)

AF:

0.318

AC:

10577

AN:

33272

American (AMR)

AF:

0.0485

AC:

2167

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0898

AC:

2345

AN:

26120

East Asian (EAS)

AF:

0.169

AC:

6706

AN:

39668

South Asian (SAS)

AF:

0.216

AC:

18613

AN:

86110

European-Finnish (FIN)

AF:

0.0209

AC:

1114

AN:

53378

Middle Eastern (MID)

AF:

0.0986

AC:

567

AN:

5750

European-Non Finnish (NFE)

AF:

0.0324

AC:

35929

AN:

1109146

Other (OTH)

AF:

0.0774

AC:

4663

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

3449

6897

10346

13794

17243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1692

3384

5076

6768

8460

<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:

0.123

AC:

18780

AN:

152204

Hom.:

2209

Cov.:

AF XY:

0.124

AC XY:

9205

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.305

AC:

12647

AN:

41494

American (AMR)

AF:

0.0734

AC:

1122

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0929

AC:

322

AN:

3466

East Asian (EAS)

AF:

0.148

AC:

767

AN:

5182

South Asian (SAS)

AF:

0.226

AC:

1091

AN:

4830

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10610

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0346

AC:

2354

AN:

68016

Other (OTH)

AF:

0.124

AC:

262

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

750

1499

2249

2998

3748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.0633

Hom.:

368

Bravo

AF:

0.133

Asia WGS

AF:

0.238

AC:

829

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.2

(source)

DANN

Benign

0.65

PhyloP100

-1.0

PromoterAI

0.0012

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over