NM_006475.3:c.607-336T>C

Variant names:

• chr13-37587264-A-G
• rs9576308
• NM_006475.3:c.607-336T>C

Variant summary

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

The NM_006475.3(POSTN):​c.607-336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,984 control chromosomes in the GnomAD database, including 25,516 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 (25516 hom., cov: 32)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 3 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.607-336T>C		intron_variant	Intron 5 of 22	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.607-336T>C		intron_variant	Intron 5 of 22	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87335 AN: 151866 Hom.: 25486 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.575 AC: 87415 AN: 151984 Hom.: 25516 Cov.: 32 AF XY: 0.573 AC XY: 42590 AN XY: 74290

African (AFR) AF: 0.607 AC: 25184 AN: 41482

American (AMR) AF: 0.577 AC: 8797 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3470

East Asian (EAS) AF: 0.847 AC: 4371 AN: 5160

South Asian (SAS) AF: 0.629 AC: 3030 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5173 AN: 10546

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.543 AC: 36912 AN: 67950

Other (OTH) AF: 0.568 AC: 1195 AN: 2104

Alfa AF: 0.569 Hom.: 4472

Bravo AF: 0.585

Asia WGS AF: 0.709 AC: 2465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.0
DANN	Benign	0.90
PhyloP100		0.46
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: rs9576308; hg19: chr13-38161401; COSMIC: COSV65714402;