rs7323378

Positions:

• chr13-37579214-T-C

Variant summary

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

The NM_006475.3(POSTN):​c.1791+15A>G 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 1,607,450 control chromosomes in the GnomAD database, including 159,223 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 (14151 hom., cov: 33)
  • Exomes 𝑓: 0.44 (145072 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.1791+15A>G		intron_variant		ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.1791+15A>G		intron_variant		1	NM_006475.3	ENSP00000369071	P3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64686 AN: 151938 Hom.: 14140 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.414 AC: 103622 AN: 250162 Hom.: 22390 AF XY: 0.416 AC XY: 56328 AN XY: 135276

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.387

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.427

GnomAD4 exome AF: 0.443 AC: 644772 AN: 1455394 Hom.: 145072 Cov.: 37 AF XY: 0.441 AC XY: 319804 AN XY: 724396

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.426 AC: 64726 AN: 152056 Hom.: 14151 Cov.: 33 AF XY: 0.428 AC XY: 31791 AN XY: 74332

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.435

Alfa AF: 0.448 Hom.: 22748

Bravo AF: 0.416

Asia WGS AF: 0.290 AC: 1010 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.59

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: rs7323378; hg19: chr13-38153351; COSMIC: COSV65713118;