dbSNP rs12243497: ANXA7:c.54+83T>A (chr10-73400720-A-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_001156.5(ANXA7):c.54+83T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,132,272 control chromosomes in the GnomAD database, including 8,937 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 0.15 ( 2828 hom., cov: 32)

Exomes 𝑓: 0.088 ( 6109 hom. )

Consequence

ANXA7
NM_001156.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247

Publications

4 publications found

Variant links:

Genes affected

ANXA7 (HGNC:545): (annexin A7) Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins.The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA. An alternatively spliced cassette exon results in two mRNA transcripts of 2.0 and 2.4 kb which are predicted to generate two protein isoforms differing in their N-terminal domain. The alternative splicing event is tissue specific and the mRNA containing the cassette exon is prevalent in brain, heart and skeletal muscle. The transcripts also differ in their 3'-non coding regions by the use of two alternative poly(A) signals. Annexin VII encodes a protein with a molecular weight of approximately 51 kDa with a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Structural analysis of the protein suggests that Annexin VII is a membrane binding protein with diverse properties, including voltage-sensitive calcium channel activity, ion selectivity and membrane fusion. [provided by RefSeq, Jul 2008]

ANXA7 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 (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001156.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANXA7	NM_001156.5	MANE Select	c.54+83T>A	intron	N/A	NP_001147.1	P20073-2
ANXA7	NM_004034.4		c.54+83T>A	intron	N/A	NP_004025.1	P20073-1
ANXA7	NM_001320880.2		c.-66-2335T>A	intron	N/A	NP_001307809.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANXA7	ENST00000372921.10	TSL:1 MANE Select	c.54+83T>A	intron	N/A	ENSP00000362012.4	P20073-2
ANXA7	ENST00000372919.8	TSL:1	c.54+83T>A	intron	N/A	ENSP00000362010.4	P20073-1
ANXA7	ENST00000961271.1		c.54+83T>A	intron	N/A	ENSP00000631330.1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22901

AN:

152034

Hom.:

2801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0647

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.0883

AC:

86505

AN:

980118

Hom.:

6109

AF XY:

0.0916

AC XY:

45147

AN XY:

493008

show subpopulations

African (AFR)

AF:

0.323

AC:

6819

AN:

21088

American (AMR)

AF:

0.0942

AC:

2478

AN:

26304

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

1954

AN:

17372

East Asian (EAS)

AF:

0.284

AC:

9276

AN:

32672

South Asian (SAS)

AF:

0.218

AC:

12498

AN:

57406

European-Finnish (FIN)

AF:

0.0484

AC:

2324

AN:

48056

Middle Eastern (MID)

AF:

0.0849

AC:

379

AN:

4464

European-Non Finnish (NFE)

AF:

0.0634

AC:

46311

AN:

730564

Other (OTH)

AF:

0.106

AC:

4466

AN:

42192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3489

6978

10468

13957

17446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1858

3716

5574

7432

9290

<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:

0.151

AC:

22978

AN:

152154

Hom.:

2828

Cov.:

AF XY:

0.152

AC XY:

11297

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.317

AC:

13149

AN:

41464

American (AMR)

AF:

0.101

AC:

1546

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

395

AN:

3466

East Asian (EAS)

AF:

0.299

AC:

1545

AN:

5172

South Asian (SAS)

AF:

0.225

AC:

1086

AN:

4822

European-Finnish (FIN)

AF:

0.0448

AC:

476

AN:

10626

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0647

AC:

4399

AN:

67992

Other (OTH)

AF:

0.122

AC:

258

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

879

1758

2637

3516

4395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.115

Hom.:

234

Bravo

AF:

0.160

Asia WGS

AF:

0.263

AC:

914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.74

PhyloP100

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over