13-37591479-G-A

Variant names:

• chr13-37591479-G-A
• rs9576312
• NM_006475.3:c.283+621C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.283+621C>T		intron_variant	Intron 3 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.283+621C>T		intron_variant	Intron 3 of 22	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

African (AFR) AF: 0.608 AC: 25167 AN: 41410

American (AMR) AF: 0.578 AC: 8819 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2247 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4371 AN: 5156

South Asian (SAS) AF: 0.636 AC: 3061 AN: 4816

European-Finnish (FIN) AF: 0.498 AC: 5247 AN: 10544

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.547 AC: 37155 AN: 67920

Other (OTH) AF: 0.570 AC: 1202 AN: 2110

Alfa AF: 0.576 Hom.: 3315

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
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9576312; hg19: chr13-38165616;