Genetic Variant NM_006475.3:c.1530-61C>T (chr13-37580052-G-A) – 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.1530-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,472,556 control chromosomes in the GnomAD database, including 145,440 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 0.43 ( 14154 hom., cov: 32)

Exomes 𝑓: 0.44 ( 131286 hom. )

Consequence

POSTN
NM_006475.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0870

Publications

4 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3 link	c.1530-61C>T		intron_variant	Intron 11 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.1530-61C>T		intron_variant	Intron 11 of 22	1	NM_006475.3	ENSP00000369071.4		Q15063-1

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64668

AN:

151858

Hom.:

14143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.443

AC:

584747

AN:

1320580

Hom.:

131286

AF XY:

0.441

AC XY:

292143

AN XY:

661970

show subpopulations

African (AFR)

AF:

0.395

AC:

11863

AN:

30070

American (AMR)

AF:

0.424

AC:

17061

AN:

40242

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

8409

AN:

23860

East Asian (EAS)

AF:

0.204

AC:

7907

AN:

38818

South Asian (SAS)

AF:

0.388

AC:

30457

AN:

78514

European-Finnish (FIN)

AF:

0.496

AC:

25930

AN:

52246

Middle Eastern (MID)

AF:

0.499

AC:

2711

AN:

5432

European-Non Finnish (NFE)

AF:

0.459

AC:

457383

AN:

995948

Other (OTH)

AF:

0.415

AC:

23026

AN:

55450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

14834

29669

44503

59338

74172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13158

26316

39474

52632

65790

<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:

0.426

AC:

64708

AN:

151976

Hom.:

14154

Cov.:

AF XY:

0.428

AC XY:

31779

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.395

AC:

16381

AN:

41424

American (AMR)

AF:

0.423

AC:

6459

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3464

East Asian (EAS)

AF:

0.153

AC:

789

AN:

5168

South Asian (SAS)

AF:

0.370

AC:

1781

AN:

4820

European-Finnish (FIN)

AF:

0.511

AC:

5393

AN:

10564

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.457

AC:

31061

AN:

67960

Other (OTH)

AF:

0.436

AC:

921

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1882

3764

5646

7528

9410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.433

Hom.:

2423

Bravo

AF:

0.416

Asia WGS

AF:

0.290

AC:

1012

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.42

(source)

DANN

Benign

0.45

PhyloP100

0.087

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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