13-37593877-G-T

Variant names:

• chr13-37593877-G-T
• rs7321492
• NM_006475.3:c.219-1713C>A

Variant summary

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

The NM_006475.3(POSTN):​c.219-1713C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,424 control chromosomes in the GnomAD database, including 26,933 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 0.59 (26933 hom., cov: 33)
• Consequence: POSTN NM_006475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	NM_006475.3	MANE Select	c.219-1713C>A		intron	N/A	NP_006466.2	Q15063-1
	POSTN	NM_001286665.2		c.219-1713C>A		intron	N/A	NP_001273594.1	Q15063-5
	POSTN	NM_001330517.2		c.219-1713C>A		intron	N/A	NP_001317446.1	Q15063-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	ENST00000379747.9	TSL:1 MANE Select	c.219-1713C>A		intron	N/A	ENSP00000369071.4	Q15063-1
	POSTN	ENST00000379743.8	TSL:1	c.219-1713C>A		intron	N/A	ENSP00000369067.4	Q15063-5
	POSTN	ENST00000541179.5	TSL:1	c.219-1713C>A		intron	N/A	ENSP00000437959.1	Q15063-3

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89462 AN: 151294 Hom.: 26904 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.505

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.591 AC: 89547 AN: 151424 Hom.: 26933 Cov.: 33 AF XY: 0.589 AC XY: 43559 AN XY: 73962

African (AFR) AF: 0.653 AC: 27086 AN: 41460

American (AMR) AF: 0.582 AC: 8877 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2248 AN: 3468

East Asian (EAS) AF: 0.847 AC: 4345 AN: 5128

South Asian (SAS) AF: 0.636 AC: 3045 AN: 4788

European-Finnish (FIN) AF: 0.498 AC: 5241 AN: 10516

Middle Eastern (MID) AF: 0.511 AC: 95 AN: 186

European-Non Finnish (NFE) AF: 0.548 AC: 37037 AN: 67646

Other (OTH) AF: 0.579 AC: 1204 AN: 2080

Alfa AF: 0.581 Hom.: 3251

Bravo AF: 0.603

Asia WGS AF: 0.712 AC: 2425 AN: 3410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.24
PhyloP100		0.33
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: rs7321492; hg19: chr13-38168014; COSMIC: COSV65714413;