13-37596374-G-C

Variant names:

• chr13-37596374-G-C
• rs9576313
• NM_006475.3:c.218+810C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006475.3(POSTN):​c.218+810C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,972 control chromosomes in the GnomAD database, including 6,735 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 0.29 (6735 hom., cov: 30)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.218+810C>G		intron_variant	Intron 2 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.218+810C>G		intron_variant	Intron 2 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43423 AN: 151854 Hom.: 6728 Cov.: 30

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.286 AC: 43443 AN: 151972 Hom.: 6735 Cov.: 30 AF XY: 0.277 AC XY: 20610 AN XY: 74280

African (AFR) AF: 0.177 AC: 7360 AN: 41476

American (AMR) AF: 0.288 AC: 4391 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3466

East Asian (EAS) AF: 0.162 AC: 835 AN: 5160

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4810

European-Finnish (FIN) AF: 0.253 AC: 2672 AN: 10558

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23884 AN: 67928

Other (OTH) AF: 0.308 AC: 650 AN: 2108

Alfa AF: 0.320 Hom.: 1029

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.36
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: rs9576313; hg19: chr13-38170511; COSMIC: COSV65714417;