13-37564593-C-T

Position:

• chr13-37564593-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2432-33G>A		intron_variant		ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2432-33G>A		intron_variant		1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107299 AN: 151502 Hom.: 38411 Cov.: 30

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

GnomAD3 exomes AF: 0.686 AC: 167798 AN: 244512 Hom.: 58191 AF XY: 0.681 AC XY: 90141 AN XY: 132356

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 SAS exome AF: 0.662

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.: 18 AF XY: 0.656 AC XY: 424645 AN XY: 647326

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.713

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.870

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.737

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.708 AC: 107386 AN: 151622 Hom.: 38448 Cov.: 30 AF XY: 0.717 AC XY: 53112 AN XY: 74068

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.689

Alfa AF: 0.651 Hom.: 54277

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
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs4390468; hg19: chr13-38138730; COSMIC: COSV65711911; COSMIC: COSV65711911;