13-37591479-G-A

Position:

• chr13-37591479-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.283+621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,888 control chromosomes in the GnomAD database, including 25,721 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 0.58 (25721 hom., cov: 31)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.283+621C>T		intron_variant		ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.283+621C>T		intron_variant		1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87702 AN: 151770 Hom.: 25691 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87782 AN: 151888 Hom.: 25721 Cov.: 31 AF XY: 0.576 AC XY: 42765 AN XY: 74248

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.570

Alfa AF: 0.574 Hom.: 3162

Bravo AF: 0.588

Asia WGS AF: 0.709 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.30

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: rs9576312; hg19: chr13-38165616;