rs9603226

chr13-37569449-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POSTN	NM_006475.3	c.2348-66C>T		intron_variant		ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9	c.2348-66C>T		intron_variant		1	NM_006475.3	P3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21337 AN: 151824 Hom.: 1659 Cov.: 32

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.: 15 AF XY: 0.119 AC XY: 65426 AN XY: 549622

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.141 AC: 21349 AN: 151942 Hom.: 1661 Cov.: 32 AF XY: 0.145 AC XY: 10803 AN XY: 74292

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.135

Alfa AF: 0.114 Hom.: 2017

Bravo AF: 0.140

Asia WGS AF: 0.211 AC: 732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.8
Dann	Benign	0.69

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: rs9603226; hg19: chr13-38143586; COSMIC: COSV65713191; COSMIC: COSV65713191;