Genetic Variant POSTN:c.2432-33G>A (chr13-37564593-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_006475.3(POSTN):c.2432-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,435,422 control chromosomes in the GnomAD database, including 316,504 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 0.71 ( 38448 hom., cov: 30)

Exomes 𝑓: 0.66 ( 278056 hom. )

Consequence

POSTN
NM_006475.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0920

Publications

13 publications found

Variant links:

Genes affected

POSTN (HGNC:16953): (periostin) This gene encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. The encoded protein binds to integrins to support adhesion and migration of epithelial cells. This protein plays a role in cancer stem cell maintenance and metastasis. Mice lacking this gene exhibit cardiac valve disease, and skeletal and dental defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

POSTN 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 (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3 link	c.2432-33G>A		intron_variant	Intron 21 of 22	ENST00000379747.9	NP_006466.2	Q15063-1A0A024RDS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9 link	c.2432-33G>A		intron_variant	Intron 21 of 22	1	NM_006475.3	ENSP00000369071.4		Q15063-1

Frequencies

GnomAD3 genomes

AF:

0.708

AC:

107299

AN:

151502

Hom.:

38411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.728

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.837

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.691

GnomAD2 exomes

AF:

0.686

AC:

167798

AN:

244512

AF XY:

0.681

show subpopulations

Gnomad AFR exome

AF:

0.802

Gnomad AMR exome

AF:

0.715

Gnomad ASJ exome

AF:

0.501

Gnomad EAS exome

AF:

0.830

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.651

Gnomad OTH exome

AF:

0.664

GnomAD4 exome

AF:

0.656

AC:

842228

AN:

1283800

Hom.:

278056

Cov.:

AF XY:

0.656

AC XY:

424645

AN XY:

647326

show subpopulations

African (AFR)

AF:

0.797

AC:

23458

AN:

29450

American (AMR)

AF:

0.713

AC:

30701

AN:

43048

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

12515

AN:

24920

East Asian (EAS)

AF:

0.870

AC:

33514

AN:

38500

South Asian (SAS)

AF:

0.661

AC:

53365

AN:

80774

European-Finnish (FIN)

AF:

0.737

AC:

39015

AN:

52966

Middle Eastern (MID)

AF:

0.679

AC:

3662

AN:

5396

European-Non Finnish (NFE)

AF:

0.640

AC:

610597

AN:

954310

Other (OTH)

AF:

0.650

AC:

35401

AN:

54436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

11925

23850

35776

47701

59626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15258

30516

45774

61032

76290

<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:

0.708

AC:

107386

AN:

151622

Hom.:

38448

Cov.:

AF XY:

0.717

AC XY:

53112

AN XY:

74068

show subpopulations

African (AFR)

AF:

0.792

AC:

32808

AN:

41410

American (AMR)

AF:

0.710

AC:

10827

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1770

AN:

3466

East Asian (EAS)

AF:

0.837

AC:

4299

AN:

5136

South Asian (SAS)

AF:

0.671

AC:

3235

AN:

4818

European-Finnish (FIN)

AF:

0.755

AC:

7954

AN:

10534

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.652

AC:

44172

AN:

67702

Other (OTH)

AF:

0.689

AC:

1448

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1585

3169

4754

6338

7923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.665

Hom.:

133132

Bravo

AF:

0.707

Asia WGS

AF:

0.739

AC:

2565

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.9

(source)

DANN

Benign

0.76

PhyloP100

0.092

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

Computational scores

Splicing

Publications

Other links and lift over