13-37574756-C-T

Position:

• chr13-37574756-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.2009-104G>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 1,362,702 control chromosomes in the GnomAD database, including 300,677 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 0.69 (36639 hom., cov: 27)
  • Exomes 𝑓: 0.66 (264038 hom.)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2009-104G>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.2009-104G>A		intron_variant		1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.695 AC: 104540 AN: 150426 Hom.: 36611 Cov.: 27

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.658 AC: 797424 AN: 1212164 Hom.: 264038 AF XY: 0.658 AC XY: 391246 AN XY: 595030

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.695 AC: 104611 AN: 150538 Hom.: 36639 Cov.: 27 AF XY: 0.705 AC XY: 51794 AN XY: 73494

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.680

Alfa AF: 0.555 Hom.: 1548

Bravo AF: 0.692

Asia WGS AF: 0.733 AC: 2538 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.35

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: rs8000073; hg19: chr13-38148893;