rs7986347

chr13-37580052-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.92).
• 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/exons	MANE	UniProt
POSTN	NM_006475.3	c.1530-61C>T		intron_variant		ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9	c.1530-61C>T		intron_variant		1	NM_006475.3	P3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64668 AN: 151858 Hom.: 14143 Cov.: 32

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

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.426 AC: 64708 AN: 151976 Hom.: 14154 Cov.: 32 AF XY: 0.428 AC XY: 31779 AN XY: 74268

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.436

Alfa AF: 0.434 Hom.: 2365

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
Dann	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs7986347; hg19: chr13-38154189; COSMIC: COSV65712986;