Genetic Variant POSTN:c.2009-104G>A (chr13-37574756-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.2009-104G>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 1,362,702 control chromosomes in the GnomAD database, including 300,677 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 0.69 ( 36639 hom., cov: 27)

Exomes 𝑓: 0.66 ( 264038 hom. )

Consequence

POSTN
NM_006475.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.938

Publications

2 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:

Genome browser will be placed here

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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3 link	c.2009-104G>A		intron_variant	Intron 16 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.2009-104G>A		intron_variant	Intron 16 of 22	1	NM_006475.3	ENSP00000369071.4		Q15063-1

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

104540

AN:

150426

Hom.:

36611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.733

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.838

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.683

GnomAD4 exome

AF:

0.658

AC:

797424

AN:

1212164

Hom.:

264038

AF XY:

0.658

AC XY:

391246

AN XY:

595030

show subpopulations

African (AFR)

AF:

0.752

AC:

19012

AN:

25270

American (AMR)

AF:

0.704

AC:

10670

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

9147

AN:

18206

East Asian (EAS)

AF:

0.875

AC:

28559

AN:

32644

South Asian (SAS)

AF:

0.663

AC:

37901

AN:

57142

European-Finnish (FIN)

AF:

0.733

AC:

22967

AN:

31350

Middle Eastern (MID)

AF:

0.667

AC:

2267

AN:

3398

European-Non Finnish (NFE)

AF:

0.648

AC:

633799

AN:

978324

Other (OTH)

AF:

0.653

AC:

33102

AN:

50670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12808

25616

38423

51231

64039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17152

34304

51456

68608

85760

<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:

0.695

AC:

104611

AN:

150538

Hom.:

36639

Cov.:

AF XY:

0.705

AC XY:

51794

AN XY:

73494

show subpopulations

African (AFR)

AF:

0.744

AC:

30608

AN:

41120

American (AMR)

AF:

0.708

AC:

10675

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1765

AN:

3454

East Asian (EAS)

AF:

0.838

AC:

4292

AN:

5122

South Asian (SAS)

AF:

0.669

AC:

3200

AN:

4780

European-Finnish (FIN)

AF:

0.756

AC:

7831

AN:

10358

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.653

AC:

43946

AN:

67328

Other (OTH)

AF:

0.680

AC:

1422

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1578

3155

4733

6310

7888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.574

Hom.:

1779

Bravo

AF:

0.692

Asia WGS

AF:

0.733

AC:

2538

AN:

3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.9

(source)

DANN

Benign

0.35

PhyloP100

0.94

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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