Genetic Variant POSTN:c.2348-66C>T (chr13-37569449-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.2348-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,222,192 control chromosomes in the GnomAD database, including 10,436 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 0.14 ( 1661 hom., cov: 32)

Exomes 𝑓: 0.12 ( 8775 hom. )

Consequence

POSTN
NM_006475.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.463

Publications

12 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POSTN	NM_006475.3	MANE Select	c.2348-66C>T	intron	N/A	NP_006466.2
POSTN	NM_001286665.2		c.2267-66C>T	intron	N/A	NP_001273594.1
POSTN	NM_001330517.2		c.2347+295C>T	intron	N/A	NP_001317446.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POSTN	ENST00000379747.9	TSL:1 MANE Select	c.2348-66C>T	intron	N/A	ENSP00000369071.4
POSTN	ENST00000379743.8	TSL:1	c.2267-66C>T	intron	N/A	ENSP00000369067.4
POSTN	ENST00000541179.5	TSL:1	c.2266+295C>T	intron	N/A	ENSP00000437959.1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21337

AN:

151824

Hom.:

1659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.118

AC:

126657

AN:

1070250

Hom.:

8775

Cov.:

AF XY:

0.119

AC XY:

65426

AN XY:

549622

show subpopulations

African (AFR)

AF:

0.172

AC:

4319

AN:

25058

American (AMR)

AF:

0.137

AC:

5785

AN:

42190

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

2688

AN:

23124

East Asian (EAS)

AF:

0.335

AC:

12607

AN:

37648

South Asian (SAS)

AF:

0.132

AC:

10074

AN:

76514

European-Finnish (FIN)

AF:

0.153

AC:

7977

AN:

52300

Middle Eastern (MID)

AF:

0.119

AC:

590

AN:

4952

European-Non Finnish (NFE)

AF:

0.101

AC:

76626

AN:

761056

Other (OTH)

AF:

0.126

AC:

5991

AN:

47408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

5495

10990

16484

21979

27474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2406

4812

7218

9624

12030

<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:

0.141

AC:

21349

AN:

151942

Hom.:

1661

Cov.:

AF XY:

0.145

AC XY:

10803

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.165

AC:

6842

AN:

41508

American (AMR)

AF:

0.144

AC:

2198

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

422

AN:

3466

East Asian (EAS)

AF:

0.343

AC:

1770

AN:

5156

South Asian (SAS)

AF:

0.158

AC:

761

AN:

4828

European-Finnish (FIN)

AF:

0.161

AC:

1705

AN:

10580

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.107

AC:

7275

AN:

67822

Other (OTH)

AF:

0.135

AC:

284

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

923

1846

2770

3693

4616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.116

Hom.:

3237

Bravo

AF:

0.140

Asia WGS

AF:

0.211

AC:

732

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.69

PhyloP100

-0.46

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