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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANXA6	NM_001155.5 link	c.1839+19G>A	intron_variant	Intron 24 of 25	ENST00000354546.10	NP_001146.2	P08133-1A0A0S2Z2Z6
ANXA6	NM_001363114.2 link	c.1821+19G>A	intron_variant	Intron 23 of 24		NP_001350043.1
ANXA6	NM_001193544.2 link	c.1743+19G>A	intron_variant	Intron 23 of 24		NP_001180473.1	P08133-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10 link	c.1839+19G>A		intron_variant	Intron 24 of 25	1	NM_001155.5	ENSP00000346550.5		P08133-1

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

Gnomad4 AFR exome

AF:

0.318

AC:

10577

AN:

33272

Gnomad4 AMR exome

AF:

0.0485

AC:

2167

AN:

44710

Gnomad4 ASJ exome

AF:

0.0898

AC:

2345

AN:

26120

Gnomad4 EAS exome

AF:

0.169

AC:

6706

AN:

39668

Gnomad4 SAS exome

AF:

0.216

AC:

18613

AN:

86110

Gnomad4 FIN exome

AF:

0.0209

AC:

1114

AN:

53378

Gnomad4 NFE exome

AF:

0.0324

AC:

35929

AN:

1109146

Gnomad4 Remaining exome

AF:

0.0774

AC:

4663

AN:

60248

Heterozygous variant carriers

3449

6897

10346

13794

17243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.305

AC:

0.304791

AN:

0.304791

Gnomad4 AMR

AF:

0.0734

AC:

0.0734005

AN:

0.0734005

Gnomad4 ASJ

AF:

0.0929

AC:

0.0929025

AN:

0.0929025

Gnomad4 EAS

AF:

0.148

AC:

0.148012

AN:

0.148012

Gnomad4 SAS

AF:

0.226

AC:

0.22588

AN:

0.22588

Gnomad4 FIN

AF:

0.0177

AC:

0.0177191

AN:

0.0177191

Gnomad4 NFE

AF:

0.0346

AC:

0.0346095

AN:

0.0346095

Gnomad4 OTH

AF:

0.124

AC:

0.123936

AN:

0.123936

Heterozygous variant carriers

750

1499

2249

2998

3748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.2

DANN

Benign

0.65

Mutation Taster

=100/0

polymorphism (auto)

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over